Pathology Flashcards
1
Q
What are the three main purines?
A
- Adenosine
- Guanosine
- Inosine
2
Q
Describe Purine Catabolism?
A
Purines
|
Hypo - Xanthine
| Xanthine Oxidase
Xanthine
| Xanthine Oxidase
Urate
| URICASE (not in humans)
Allantoin
3
Q
Why can humans not break down Urate into Allantoin?
A
The Uricase gene is inactive.
4
Q
What are the Monosodium urate plasma concentrations?
A
- Men: 0.12-0.42 mmol/L
- Women: 0.12-0.36 mmol/L
Solubility at 37 degrees: 0.40 mmol/L
=> men get more gout than women
Solubility at 30 degrees: 0.27 mmol/L
=> first metatarsophalangeal joint most commonly affected due to cooler peripheries.
5
Q
What happens to uric acid in the PCT.
A
It is absorbed AND excreted.
*Only 10% of filtered urate will be present in the urine.
= Fractional Excretion of Uric Acid (FEUA)
6
Q
Inosinic acid (IMP) is an intermediate metabolite for which two chemical messengers in the purine metabolic pathway?
A
adenylic acid (AMP) and guanylic acid (GMP）
7
Q
What are the two ways of making purines?
A
De novo synthesis or the salvage pathway
8
Q
Describe De Novo synthesis
A
Ribose-5-Phosphate is converted to inosinic acid through a number of intermediaries.
- The rate limiting step is catalysed by PAT (PPRP ==> inosinic acid)
- outputs = IMP, GMP and AMP
- GMP and AMP give -ve feedback to PAT
- PPRP give +ve feedback to PAT
NB: this method is metabolically demanding and inefficient so the forces of evolution will generally mitigate against using de novo metabolism
EXCEPT, when there is a very high demand for purines
The only tissue where DNS predominates is the BONE MARROW due to high levels of cell synthesis
9
Q
Describe the Salvage Pathway
A
HPRT (aka HGPRT)
- Hypoxanthine-guanine phosphoribosyltransferase-
This enzyme will scoop up partially catabolised purines and bring them back up the metabolic pathway to produce IMP and GMP
Main reactions:
- Hypoxanthine –> IMP
- Guanine –> GMP
This is a form of recycling and it is highly energy efficient.
This is the PREDOMINANT pathway in purine synthesis.
Pretty much all cells in the body can produce purines via this pathway .
10
Q
What is the name of HGPRT deficiency.
A
Lesch-Nyhan Syndrome (absolute deficiency)
11
Q
What is the inheritance of Lesch-Nyhan Syndrome?
A
This is an X-linked disease (almost exclusively affects boys)
Affects 1 in 40,000 live births
12
Q
What are the clinical features of Lesch-Nyhan Syndrome?
A
- Normal @ birth
- Developmental delay at 6 months
- Hyperuricaemia (very rare in children)
- Choreiform movements (at 1 year)
- Spasticity and mental retardation
KEY FEATURE: Self-mutilation in 85% of patients at ages 1-16 (e.g. biting lips very hard)
13
Q
What is the biochemical basis for Lesch-Nyhan Syndorme?
A
ABSOLUTE HGPRT deficiency
1. no guanine will be converted back to GMP, and no hypoxanthine will be converted to IMP
- As there is less IMP And GMP being produced, there is less inhibitory feedback to PAT
- This means that the de novo pathway goes into overdrive
- Therefore, your cells will start to uncontrollably make IMP
- As there is so much IMP being produced via the de novo pathway, lots of it will get shunted down the catabolic pathway leading to an accumulation of urate
- Furthermore, because there is less guanine being converted to GMP, PPRP builds up - this is another factor driving PAT via positive feedback .
14
Q
Name some causes of increased urate production?
A
PRIMARY:
- Partial HPRT deficiency
- Absolute HPRT deficiency (Lesch-Nyhan Syndrome)
SECONDARY:
- High cell turnover
e. g. myeloproliferative/lymphoproliferative disorders
e. g. chronic haemolytic anaemia - Decreased urate exretion
e. g. CKD
e. g. drug (DIURETICS, aspirin)
15
Q
Name some causes of decreased urate production
A
- Decreased urate production
- Xanthine oxidase deficiency
- ALLOPURINOL
- Increased urate excretion
- Idiopathic hypouricaemia
NB: very few clinical implications of low urate.
16
Q
What is gout?
A
Monosodium urate crystals
These crystals are powerful inflammatory stimuli for inflammatory cells, which can trigger an intense inflammatory reaction in the synovium of the joint
Acute = PODAGRA Chronic = TOPHACEOUS
Tophi tend to be found on the fingers and on the pinna of the ear. You can get some periosteal erosion due to the presence of a tophus
Prevalence:
Males: 0.5-3%
Females: 0.1-0.6%
Tends to affect post-pubertal males and post-menopausal females
17
Q
Clinical Features of Acute Gout
A
- Raised shiny lump
- Rapid build up of ‘exquisite’ pain
- Affected joint is red, hot and swollen
- Peri-osteal erosion)
1st MTP (big toe) is the first site affected in 50% 1st MTP is involved in 90% of cases
18
Q
How is gout diagnosed?
A
Tap effusion
- view under polarised light
- use red filter
Needle-shaped and negatively birefringent
(Blue perpendicular to the direction of the light)
19
Q
What is birefringence?
A
the ability of a crystal to rotate the axis of the polarised light
Urate - Needle-shaped and Negatively birefringent
*NEGATIVELY birefringent crystals will appear BLUE and at 90 degrees to the axis of the red compensator
Calcium Pyrophosphate - Rhomboid-shaped and positively birefringent
POSITIVELY birefringent crystals will appear BLUE in the axis of the red compensator
20
Q
What are the two main goals when managing gout?
A
- Reducing inflammation
- Managing hyperuricaemia
21
Q
How do you manage acute gout?
A
REDUCE INFLAMMATION
- NSAIDs
- Colchicine
- Glucocorticoids
IMPORTANT: you should NOT try to modify the plasma urate concentration at that stage, because it could actually lead to further urate deposition
22
Q
How do you manage chronic/post-acute gout?
A
- Drink lots of water
- Reverse factors that are increasing the circulating uric acid concentration (e.g. stopping diuretics)
- Reduce synthesis of urate with allopurinol (xanthine oxidase inhibitor)
- Increase renal excretion of urate with probenecid (uricosuric)
NB: Uricosuric drugs will increase the FEUA
23
Q
What are the side-effects of Allopurinol?
A
NEVER give it to someone who is on azathioprine
Allopurinol interacts with azathioprine (reduces metabolism), making it more toxic to the bone marrow
24
Q
How does Colchicine work?
A
inhibiting the manufacture of tubulin
= reduces mitosis
= reduce the motility of neutrophils (less inflammation)
25
What is pseudogout?
Calcium pyrophosphate crystals
*Rhomboid-shaped and positively birefringent *
Occurs in patients with osteoarthritis
Self-limiting and lasts 1-3 weeks
26
What is the normal life span of a red cell?
120 days
27
How can haemolysis be classified?
* Intravascular or extravascular
| * Inherited or acquired
28
Name some causes of extravascular haemolysis (in the reticuloendothelial system) ?
- Autoimmune
- Alloimmune
- Hereditary Spherocytosis
==> Autosomal dominant, increased lysis in hypotonic saline
29
Name some causes of intravascular haemolysis (in the circulation) ?
- Malaria
- G6PD Deficiency
- Mismatched blood transfusion
- Cold antibody haemolytic syndromes
- Drugs
- Microangiopathic haemolytic anaemias e.g. haemolytic uraemic syndrome, thrombotic thrombocytopaenia purpura
- Paroxysmal nocturnal haemoglobinuria
30
Most common cause of intravascular haemolysis?
Malaria
NB: G6PD deficiency offers a degree of protection against malaria (so it is a common genetic disease worldwide)
31
Example of a drug that causes intravascular haemolysis?
Dapsone
Abx used to treat leprosy
32
What causes Paroxysmal nocturnal haemoglobinuria?
an acquired genetic defect in the glycosylphosphatidylinositol anchor (GPI anchor) which is one of the two principle mechanisms by which cells attach proteins to their surface
33
How can we classify Hereditary Haemolytic Anaemias?
Can be divided into disorders affecting the:
* Membrane :
- Cytoskeletal proteins
- Cation permeability
*Red cell metabolism
(Particularly glycolysis)
* Haemoglobin
- Thalassemia
- Sickle cell syndromes
- Unstable Hb variants
34
What are the consequence of haemolysis?
- Anaemia
NOTE: this is NOT always the case, because the output of red cells from the bone marrow may compensate fully for the haemolysis
- Erythroid hyperplasia
With increased red cell production and increased reticulocytes
- Increased folate demand
NOTE: folate supplementation may be given to some patients with haemolytic anaemias
- Susceptibility to the effect of parvovirus B19
- Propensity to gallstones
Due to increased generation of bilirubin
- Increased risk of iron overload
This can be due to increased intestinal iron absorption (not necessarily because they are being transfused)
- Increased risk of osteoporosis
35
Why does parvovirus affect people with haemolytic anaemia?
The virus has the ability to infect erythroid cells in the bone marrow and arrest their maturation (in the image, all the cells are at the same stage of maturation)
If this happens to someone with normal red cell survival, it has little impact on the Hb concentration
However, if this happens to someone with shortened red cell life span (e.g. 5-7 days) this can cause a dangerously low Hb (aplastic crisis)
This is self-limiting as the virus will eventually resolve
**This can be identified very quickly by observing a low reticulocyte count (showing that red cell production has been switched off)**
36
Clinical features of haemolysis
* Anaemia
- Pallor, jaundice
* Splenomegaly
particularly prominent in conditions characterised by extra-vascular haemolysis
* Pigmenturia
* Family History
37
Laboratory features of haemolysis
* Anaemia
* Increased reticulocytes
* Polychromasia
an appearance where cells take up both the eosinophilic and basophilic dye and have a bluish appearance. This is due to the presence of reticulocytes
* Hyperbilirubinaemia
INTRAVASCULAR HAEMOLYSIS:
* Increased LDH
LDH is an enzyme that is present in high concentrations within red blood cells, so increased plasma LDH concentrations will occur if there is intravascular haemolysis
* Reduced/absent haptoblobins
Haptoglobin = a protein present in the blood stream which binds to and removes free haemoglobin from the bloodstream. So, low haptoglobins would suggest that there are high levels of free haemoglobin in the blood stream
* Haemoglobinuria
can be assessed by visual inspection
* Haemosiderinuria
requires a special stain (e.g. Perl's stain or Prussian blue)
38
Which proteins are involved in hereditary spherocytosis?
Proteins that are involved in vertical interaction (between proteins that link the lipid bilayer to the cytoskeleton)
- Band 3
- Protein 4.2
- Ankyrin
- beta-Spectrin
39
What are the clinical features of hereditary spherocytosis?
* Hb lacks central pallor (not biconcave)
* Hb smaller
* Darker stain
* MCHC ++
* reticulocytosis
NB: MOST COMMON genetic defect of the red cell cytoskeleton.
NB: 75% have FH
40
Dx of hereditary cytosis
**Osmotic Fragility Test**
the hallmark of red cells in hereditary spherocytosis is that they show increased sensitivity to lysis in hypotonic saline
NB: The cells also show reduced binding of the dye, eosin-5-maleimide.This is determined using flow cytometry. The test sample has lower binding than the control
41
Which proteins are involved in hereditary elliptocytosis?
Proteins that are involved in horizontal interaction
- alpha-spectrin
- beta-spectrin
- Protein 4.1
42
What are the clinical features of Hereditary Pyropoikilocytosis (HOMOZYGOUS form of hereditary eliptocytosis)
* Elongated red cells (elliptocytes)
* A lot of fragmentation of red cells
* There is a lot of poikilocytosis (variation in shape of red cells)
This condition can cause severe haemolytic anaemia
43
Where is G6PD deficiency commonly found?
Areas where malaria is endemic
44
What is the mode of inheritance for G6PD deficiency?
X linked
The most severe phenotypes are:
* Hemizygous males
* Homozygous females
45
What are the clinical features of G6PD deficiency?
* Neonatal jaundice
* Acute haemolysis (oxidant/infective triggers)
* Chronic haemolytic anaemia
46
How does G6PD deficiency lead to red cell destruction?
1. G6PD enzyme catalyses the first step in the pentose phosphate (hexose monophosphate) pathway
NOTE: It plays a relatively minor part in glycolysis within the red cell
2. This reaction generates NADPH which is required to maintain intracellular glutathione (GSH)
3. Glutathione is needed to protect the red cell against oxidative stress
**KEY POINT: red cells that are deficient in glutathione, are vulnerable to damage by oxidative stress**
47
What are the triggers for acute haemolysis in G6PD deficiency?
1. Drugs
- Antimalarials (primaquine)
- Antibiotics (sulphonamides, ciprofloxacin, nitrofurantoin)
- Dapsone
- Vitamin K
2. Infections
3. Fava beans
4. Naphthalene mothballs
48
What might you see on the blood film of a pt with acute haemolysis due to G6PD deficiency?
* contracted cells
* nucleated red cells
* bite cells (cells that look like they've had part of their cytoplasm removed)
* hemighosts (haemoglobin is retracted to one side of the cell)
49
What might you see on the blood film of a pt with pyruvate kinase deficiency?
* echinocytes (red cells with short projections)
NB: as the cells decrease in size due to dehydration, the cells will come to resemble spherocytes
NB: The # of echinocytes increases post-splenectomy
50
What pathway is defective in pyruvate kinase deficiency?
The glycolytic pathway
51
What are the first line investigations for haemolytic anaemia?
1. DAT
= check for autoimmune haemolysis
2. Urinary haemosiderin/haemoglobin
= suggests intravascular haemolysis
NB: High LDH and low haptoglobin also suggest intravascular haemolysis
3. Osmotic fragility
= suggest hereditary spherocytosis
NB: the dye binding test is used more frequently now
4. G6PD +/- PK activity
* G6PD = episodic
* PK = chronic haemolytic anaemia
5. Hb separation of A and F%
6. Heinz-body stain
= suggests oxidative haemolysis
7. Ham's test/Flow cytometry of GPI linked proteins
Ham's test looks @ sensitivity of red cells to lysis by acidified serum
= paroxysmal nocturnal haemoglobinuria
8. Thick and thin blood film
= check for malaria
52
What are the management options for haemolytic anaemia.
1. folic acid supplementation
2. avoidance of precipitating factors (e.g. oxidants in G6PD deficiency)
3. Red cell transfusions/exchange
4. imms against blood borne viruses (e.g. Hep B)
= [more likely to receive blood products]
5. Monitor for chronic complications (e.g. gallstones, iron overload, osteoporosis)
6. Cholecystectomy for symptomatic gallstones
NB: w/ Gilbert's consider prophylatic cholecystectomy
7. Splenectomy
53
Indications of splenectomy in haemolytic anaemia?
* PK deficiency + some other enzymopathies
* Hereditary spherocytosis
* Severe eliptocytosis/pyropoikilocytosis
* Thalasseamia syndromes
* Immune haemolytic anaemia
54
What are the risks of splenectomy
1. risk of overwhelming SEPSIS
2. susceptible to capsulate bacteria (e.g. pneumococcus)
**risk can be reduced by penicillin prophylaxis and appropriate imms**
55
What is the specific criteria for splenectomy?
1. Transfusion dependence
2. Growth delay
3. Physical limitation (usually when Hb <8 g/dL
4. Hypersplenism (to the extent where it causes pooling and physical symptoms)
5. Age >3 years
6. Age <10 years to maximise prepubertal growth
56
What do neutrophils look like on a blood film?
- multi-lobed
| - granules
57
What are neutrophils associated with?
acute inflammation
58
What do lymphocytes look like on a blood film?
- little cytoplasm and big nucleus
59
What are lymphocytes associated with?
chronic inflammation (and lymphomas
60
What do eosinophils look like on a blood film?
- bi-lobed nucleus with red granules
61
What are eosinophils associated with?
1. allergic reactions (e.g. asthma, drug hypersensitivity)
2. parasite infections
3. Tumours (e.g. Hodgkin's disease
NB: the eosinophils are NOT the malignant cells
62
What do mast cells like on a blood film?
Large and contain lots of granules (no cytoplasm)
63
What do macrophages look like on a blood film?
Lots of cytoplasm with a granulated area (containing lytic enzymes)
64
What are macrophages associated with?
1. Late acute inflammation
= cells that come to clear debris
2. Chronic inflammation (incl. granulomas
65
Whats is a granuloma?
an organised collection of activated macrophages
- the macrophages are secretory (as opposed to phagocytic)
- they have a lot more cytoplasm making them look like epithelial cells, so these activated macrophages are describes as epithelioid macrophages
66
How can you tell whether a sputum sample has come from the lungs (as opposed to the upper airway)?
pigmented macrophages
67
What are the causes of granulomas?
1. TB
2. Leprosy
3. Cat scratch fever
4. Fungal infections
5. Sarcoidosis (idiopathic granuloma)
68
What should you do if you find a granuloma in the lung?
Ziehl-Neelson stain to check for acid-fast bacilli
| test for TB
69
What are the types of tumour?
1. Carcinoma (epithelial cells)
2. Sarcoma
3. Lymphoma
4. Melanoma
NB: tumours are defined based on their presumed origins)
70
How do you identify squamous cell carcinomas?
1. Keratin production
NB: not all SE produce keratin (e.g. oesophagus)
2. Intercellular bridges
71
How do you identify adenocarcinomas?
1. mucin production
| 2. glands
72
What are the three types of carcinoma?
1. squamous cell carcinoma
2. adenocarcinomas
3. transitional cell carcinomas
73
What are the sites of origin for squamous cell carcinomas?
1. skin
2. head and neck
3. oesophagus
4. anus
5. cervix
6. vagina
74
What can you see in glandular epithelium?
- crypts
75
What can you see when you stain glandular epithelium
- mucin within the gland (blue)
| - goblet cells
76
What are the sites of origin for adenocarcinoma?
1. lung
2. breast
3. stomach
4. colon
5. pancreas
77
What stain is used for melanin (to diagnosis melanoma)?
Fontana stain
melanin appears brown
78
What are the types of stain?
1. Histochemical
- Based on the chemical reaction between the stain and the tissue
- the product of the reaction has a specific colour, or other property that can be identified
2. Immunohistochemical
- involves using antibodies against a specific antigen present in a tumour
- some kind of detection system is used to show up these antibodies (and hence the antigens)
79
What is the stain for iron?
Prussian blue
80
Give an example of a histochemical stain?
Haematoxylin and Eosin
Part of it will bind to the acid part of the tissue, and part of it will bind to the basic part of the tissue. Often used as the stain of choice?
81
What is the stain or amyloid?
Congo Red
82
What happens when you put Congo Red stain under polarised light?
If there is amyloidosis, it will produce apple green birefringence
83
What are two mechanisms of immunohistochemistry?
1, immunofluorescence
= adding a fluorescent tag to the antibody
2. immunoperoxidase
= adding an enzyme that binds to the antibody and a substrate that causes a colour change
84
What does the cytokeratin antibody detect?
cytokeratin.
This is a characteristic feature of ALL epithelial cells.
85
What does CD45 detect?
lymphoid tissue
86
What is the classic histopathological feature of herpes simplex virus.
Polynucleated cells.
87
Identify the disease?
minor skin abrasion => bacillus anthracis
cutaneous anthrax
88
Identify the disease?
puncture wound => clostridium tetani
Tetanus
89
Identify the disease?
handling infected animals => francisella tularensis
Tuleraemia
90
Identify the disease?
Mosquito bites (aedes aegypti) => flavivirus
Yellow fever
91
Identify the disease?
Deer tick bites => borella burgdorteri
Lyme disease
92
Identify the disease?
Mosquito bites (anopheles) => Plasmodium spp.
Malaria
93
Identify the disease?
inhaled spores => Neisseria meningitidis
meningococcal meningitis
94
Identify the disease?
inhaled spores => bacialla anthracis
inhalation anthrax
95
Identify the disease?
contaminated water/food => salmonella thypi
typhoid fever
96
Identify the disease?
contaminated water/food => rotavirus
diarrhoea
97
Identify the disease?
sexual contact => treponema pallidum
syphillis
98
Identify the disease?
sexual contact => HIV
AIDs
99
How does skin protect us from pathogens?
1. tightly packed keratinised cells
2. physical barrier
3. physiological factors
- low pH
- low oxygen tension
4. sebaceous glands, which produce:
- hydrophobic oils: repel water and microorganisms
- lysozyme: destroy the integrity of bacterial cell wall
- ammonia and defensins: have anti-bacterial properties
100
How do our mucosal surface protect us from pathogens?
1. physical barrier = traps pathogens
2. contain secretory IgA:
binds to pathogens and protects and prevents bacteria and viruses from attaching to and penetrating epithelial calls
3. lysozyme and antimicrobial peptides:
directly kill invading pathogens
4. lactoferrin starves invading bacteria of iron
5. cilia:
- directly trap pathogens
- contribute to the removal of mucus, which is assisted by physical maneuvers such as coughing and sneezing
101
How do commensal bacteria protect us from pathogens?
1. they compete with pathogenic bacteria for scarce resources
2. they produce fatty acids and bactericidins that inhibit the growth of many pathogens.
102
What are the cells of the innate immune system?
1. Polymorphonuclear cells (neutrophils, eosinophils and basophils)
2. Monocytes and macrophages
3. NK cells
4. Dendritic cells
103
What are the soluble components of the innate immune system?
1. Complement
2. Acute Phase proteins
3. Cytokines and chemokines
104
What are the key features of the innate immune system?
1. identical responses in ALL individuals
2. Cells express receptors that allow them to detect and home to site of infection
3. Cells express genetically encoded receptors - Pattern Recognition Receptors (PRRs) - that allow them to detect pathogens at the site of infection
4. Cells have phagocytic capacity that allows them to engulf pathogens
5. Cells secrete cytokines and chemokines that regulate the immune response
105
Where are polymorphonuclear cells produced?
in the bone marrow
106
What do polymorphonuclear cells do?
migrate rapidly to the side of injury
* Express receptors for cytokines/chemokines
= to detect inflammation
* Express pattern recognition receptors
= to detect pathogens
* Express Fc receptors for Ig
= to detect immune complexes
* Capable of phagocytosis/oxidative + non-oxidative killing (esp. neutrophils)
* Release enzymes, histamine, lipid mediators of inflammation from granules
* Secrete cytokines and chemokines to regulate inflammation
107
Where are monocytes produced?
bone marrow
108
How do monocytes travel?
through the blood
they migrate to tissues where they differentiate to become macrophages
109
What are the names of the macrophages in:
```
A. Liver
B. Kidney
C. Bone
D. Spleen
E. Lung
F. Neural tissue
G. Connective tissue
H. Skin
I. Joints
```
```
A. Kuppfer cell
B. Mesangial cell
C. Osteoclast
D. Sinusoidal lining cell
E. Alveolar macrophage
F. Microglia
G. Histocyte
H. Langerhans cells
I. Macrophage like synoviocytes
```
110
What is the difference between macrophages and polymorphonuclear cells?
They can process antigens and present them to T cells.
111
What can macrophages do?
* Express receptors for cytokines/chemokines
= to detect inflammation
* Express pattern recognition receptors
= to detect pathogens
* Express Fc receptors for Ig
= to detect immune complexes
* Capable of phagocytosis/oxidative + non-oxidative killing (esp. neutrophils)
* Secrete cytokines and chemokines to regulate inflammation
* Capable of presenting processed antigen to T cells
112
How does phagocyte recruitment occur?
1. cellular damage and bacterial products trigger the local production of inflammatory mediators (cytokines and chemokines)
* cytokines: activate the vascular endothelium, enhancing permeability
* chemokines: attract phagocytes
113
How are micro-organisms recognised in the innate immune system?
Pattern Recognition receptos (PRR) recognise generic motifs known as pathogen-associated molecular patterns (PAMPs) such as bacterial sugars, DNA and RNA.
PRR examples: toll-like receptors, mannose receptors
Fc receptors on these cells allows them to bind to the Fc portion of immunoglobulins thereby allowing the phagocytes to recognise immune complexes
114
How does opsonisation work?
1. Opsonins act as a bridge between the pathogen and the phagocyte receptors
2. The antibodies will bind to the Fc receptors on the phagocytes
3. Complement components can bind to complement receptors (i.e CR1)
4. Acute Phase Proteins (e.g. CRP) will also promote phagocytosis
115
How is the phagolysosome formed?
1. The pathogen is taken up by the phagosome
2. The phagosome will fuse with the lysosome
This is protected compartment in which killing of the organism occurs. The killing of the pathogen can occur by oxidative mechanisms or non-oxidative mechanisms
116
How does oxidative killing occur?
1. NADPH oxidase converts oxygen ==> reactive oxygen species (superoxide and hydrogen peroxide)
2. Myeloperoxidase catalyses the production of hydrochlorous acid from hydrogen peroxide and chloride
**Hydrochlorous acid is a highly effective oxidant and anti-microbial**
117
How does non-oxidative killing occur?
Killing by the release of bactericidal enzymes such as lactoferrin and lysozyme into the phagolysosome?
- enyzmes are present in granules
- each has a unique antimicrobial spectrum = broad range of cover against bacteria and fungi
118
What is pus?
liquified tissue caused by an adjacent accumulation of dead/dying neutrophils
this is because phagocytosis depletes glycogen reserves in the neutrophil => neutrophil death => residual enzymes cause liquefaction of adjacent tissue
119
What is an abscess?
a collection of pus?
120
What are natural killer (NK) cells?
lymphocytes that express inhibitory receptors capable of recognising HLA Class I molecules and have cytotoxic capacity
* present within the blood and may migrate to infected tissue
* Express inhibitory receptors for self HLA which prevents inappropriate activation by normal self cells
* Express a range of activatory receptors including natural cytotoxicity receptors that recognise heparan sulphate proteoglycans
* Integrate signals from inhibitory and activatory receptors (usually the inhibitory signals will dominate)
* Secrete cytokines to regulate inflammation and promote dendritic cell function
121
What are the function of dendritic cells?
* reside in peripheral tissue
* express receptors for cytokines and chemokines (to detect inflammation)
* express pathogen recognition receptors (to detect pathogens)
* express Fc receptors for immunuglobulin (to detect immune complexes)
* capable of phagocytosis
* following phagocytosis, dendritic cells will:
- upregulate expression of HLA molecules
- express co-stimulatory molecules
- migrate via lymphatics to lymph nodes (mediated by CDR7)
* present processed antigens to T cells in lymph nodes to prime the adaptive immune system
* express cytokines to regulate the immune system
122
What are the components of the adaptive immune system?
1. Humoral Components
B-lymphocytes and antibodies
2. Cellular immunity
T-lymphocytes (CD4+ and CD8+)
3. Soluble components
Chemokines and cytokines
123
What is the definition of a primary lymphoid organ?
organs involved in lymphocyte development
includes both the bone marrow + thymus. site of B cell and T cell development
124
What happens in the bone marrow (immunity)?
* immature B and T cells are derived from haematopoietic stem cells
* B cell maturation
125
What happens in the thymus (immunity)?
T cell maturation
NB: this is most active in the foetal and neonatal period, involutes after puberty
126
What is the definition of a secondary lymphoid organ?
anatomical sites of interaction between naive lymphocytes and micro-organisms
i. e.
- spleen
- lymph nodes
- MALT
127
What is the role of the thoracic duct in immunity?
Carries lymphocytes from lymph nodes back to the blood circulation
128
What is the role of the germinal centre?
Are within the secondary lymphoid tissues where B cells proliferate and undergo affinity maturation and isotope switching
129
What are the key features of the adaptive immune system?
1. Wide repertoire of antigen receptors
- receptor repertoire not entirely genetically encoded
- genes for segments of receptors are rearranged and nucleic acids deleted/added @ the sites of rearrangement almost randomly
- auto-reactive cells are likely to be generated
- mechanisms must exist to delete/tolerise these auto-reactive cells
2. Exquisite specificity
able to discriminate between very small differences in molecular structure
3. Clonal expansion
Cells with appropriate specificity will proliferate during infection
4. Immunological memory
Following infection, residual pool of specific cells with enhanced capacity to respond in re-infection occurs
130
What is the process for selection and central tolerance in the thymus for T cells?
1. Low affinity for HLA= NOT SELECTED
- to avoid inadequate reactivity
2. Intermediate affinity HLA = POSITIVE SELECTION
~ 10% of original cells ==> further development to CD4+ or CD8+ lymphocytes
3. High affinity for HLA = NEGATIVE SELECTION
- to avoid auto-reactivity
131
What peptides are recognised by CD4+ T lymphocytes?
those presented by HLA Class II
132
What peptides are recognised by CD8+ T lymphocytes?
those presented by HLA Class I
133
What type of cells are CD4+ T lymphocytes?
Helper T cells
- recognise peptides derived from extracellular proteins
134
Gives some examples of HLA Class II molecules.
1. HLA-DR
2. HLA-DP
3. HLA-DQ
135
What do Helper T cells do?
Immunoregulatory functions via cell:cell interactions and the expression of cytokines
- help for the development of a full B cell response
- help for the development of some CD8+ T cell responses
136
What type of cells are CD8+ T lymphocytes?
Cytotoxic T cells
137
Gives some examples of HLA Class I molecules.
1. HLA-A
2. HLA-B
3. HLA-C
138
What to Cytotoxic T cells do?
1. kill cells directly:
* perforin (pore-formning) and granzymes
* expression of Fas ligand
2. Secrete cytokines (e.g. IFN-gamma, TNF-alpha)
** particularly important in defence against viral infections and tumours**
139
What is T cell memory?
A pool of memory T cells that are ready to respond to an antigen on a repeat exposure. These cells are more easily activated than naive cells (quicker and more aggressive response)
140
What are Th1 cells?
Subset of cells that express CD4+ and secrete IFN gamma and IL-2
141
What are T follicular helper (Tfh) cells?
Play an important role in promoting germinal centre reactions and differentiation of B cells in to IgG and IgA secreting plasma cells.
142
What are T regulatory cells?
Subset of lymphocytes that express Foxp3 and CD25
143
What is the germinal centre?
Where IgM B cells, which exist in the periphery, differentiate and proliferate into IgG, IgE and IgA.
144
What is the process for selection and central tolerance for B cells.
1. No recognition of self in the bone marrow = SURVIVE
2. Recognition of self in bone marrow = NEGATIVE SELECTION
- to avoid autoreactivity
145
What happens when a B cell in the periphery engages an antigen?
Early IgM response = cell differentiates into an IgM secreting plasma cell
146
What cell is the germinal centre reaction dependent on?
T helper cells
147
What are the stages of the germinal centre reaction?
1. Dendritic cells will prime CD4+ T helper cells
2. CD4+ cells provide help for B cell differentiation
* *mediated by CD40L:CD40**
3. With the help of CD4+ cells, the B cells will proliferate
4. They then undergo somatic hypermutation and Isotype switching (from IgM to IgG/A/E)
5. They will then become plasma cells which produce antibodies.
148
What type of molecule are immunoglobulins?
soluble proteins made up of 2 heavy chains + 2 light chains
149
What chain determines the antibody class (GAMED)?
heavy
150
Which immunoglobulins have subclasses?
IgG and IgA
151
How is the antigen recognised by the Ig?
the antigen binding region (Fab)
this is made up of both the heavy and light chains
152
What determines the effector function of the Ig?
the constant region (Fc)
this is composed of the heavy chain
153
What are the functions of the antibodies?
1. Identification of pathogens and toxins (Fab-mediated)
2. Interact with other components of immune responses to remove pathogens (Fc-mediated)
- complement
- phagocytes
- NK cells
**particularly important in defense against bacteria of all kinds**
154
B cell memory: what are the differences in primary and secondary response?
1. Lag time between antigen exposure and antibody production is decreased (to 2-3 days)
2. Titres of antibody produced is increased
3. Response is dominated by IgG antibodies of high affinity, as opposed to primary response in which you will get an early IgM response
**NB: the response may be INDEPENDENT of help from CD4+ cells**
155
What is IgA and where is it found?
Divalent antibody present within mucous which helps provide a constitutive barrier to infection
156
What is an IgG secreting plasma cell?
A cell dependent on the presence of CD4+ help for generation
157
How are IgM secreting plasma cells generated?
they are generated rapidly following antigen recognition are not dependent on CD4+ T helper cells.
158
What is complement?
20 + tightly regulated proteins: when triggered enzymatically activate other proteins in a biological cascade = rapid, highly amplified response
* produced by the liver
* present in the circulation as INACTIVE molecules
159
What are the pathways in complement?
1. Classical pathway
2. Mannose Binding Lectin Pathway
3. Alternative Pathway
160
What are the stages of the Classical Pathway?
1. Activated by Immune complexes (w/ C4, C2, C1)
2. The formation of antibody-antigen immune complexes results in a conformational change in antibody shape which exposes the binding site for C1
3. Binding of C1 to the antibody results in the ACTIVATION OF THE CASCADE
**As it involves antibodies, DEPENDENT ON THE ACTIVATION OF THE ADAPTIVE IMMUNE RESPONSE (i.e. it will not occur early in the response)
161
What are the stages of the Mannose-Binding Lectin Pathway?
1. Activated by DIRECT BINDING of MBL => MICROBIAL CELL SURFACE CARBOHYDRATES
2. This directly stimulates the classical pathway involving C4 and C2 (but NOT C1)
** NOT DEPENDENT on the ADAPTIVE IMMUNE RESPONSE **
162
What are the stages of the Alternative Pathway?
1. DIRECTLY triggered by the binding of C3 => BACTERIAL CELL WALL COMPONENTS
e. g. lipopolysaccharide of gram-negative bacteria
e. g. teichoic acid of gram-positive bacteria
* this involves factors: B, I, P
** NOT DEPENDENT on the ADAPTIVE IMMUNE RESPONSE**
163
What is the final common pathway in complement?
C5-C9
164
What is formed at the end of complement?
The membrane attack complex
165
What protein do all of the pathways lead to before the common pathway?
C3
166
What roles do complement fragments (released through complement activation) play in the immune response?
* increase vascular permeability and cell trafficking to sites of inflammation
* opsonisation of immune complexes keep them soluble
* opsonisation of pathogens to promote phagocytosis
* activation of phagocytes
* promotes mast cells/basophils degranulation
* punch holes in bacterial membranes
167
Cleavage of this protein may be triggered by the classical, MBL and alternative pathway...
A. C3
B. C1
C. C9
D. MBL
C3
168
Binding of immune complexes to this protein triggers the classical pathway of complement activation...
A. C3
B. C1
C. C9
D. MBL
C1
169
Part of the final common pathway, resulting in the generation of the membrane attack complex...
A. C3
B. C1
C. C9
D. MBL
C9
170
Binds to microbial surface carbohydrates to activate the complement cascade in an immune complex independent manner
A. C3
B. C1
C. C9
D. MBL
MBL
171
What are cytokines and what is their function?
small protein messangers with immunomodulatory f
function
e. g. IL2, IL6, IL10, IL12, TNF-alpha, TGF-beta
* autocrine and paracrine dependent action
172
What are chemokines and what is their function?
subset of cytokines, which are involved in the direct recruitment/homing of leukocytes in an inflammatory response
e. g. CCL19 and CCL21 are ligands for CCR7 and important for directing dendritic cell trafficking to lymph nodes
e. g. IL8, RANTES, MIP1-alpha and -beta
173
What are the features of atherosclerotic lesions?
fibrous cap, foam cells and necrotic core
174
What is a foam cell?
macrophages that are full of cholestryl ester
175
What is the necrotic core made out of?
cholesterol crystals
they become deposited after the macrophages die and release enzymes that hydrolyse the cholestryl ester and convert them into free cholesterol that crystallises
176
Order the lipoproteins, biggest to smallest?
1. Chylomicrons
2. Very low density lipoproteins (VLDLs)
3. Low density lipoproteins (LDLs)
4. High density lipoproteins (HDLs)
177
Which lipoproteins are the highest in triglycerides?
Chylomicrons and VLDLs
178
Which lipoprotein is the main carrier of cholesterol?
LDL
179
Where does the cholesterol entering the intestines come from?
Bile and diet
180
What happens to cholesterol when it enters the intestines?
1. it is solubilised in mixed micelles
2. it is then transported across the intestinal epithelium by NPC1L1
**NB: this is the main determinant of cholesterol transport going into the lymphatics, and then to the liver**
181
What are the names of the transporters that transport cholesterol back into the lumen of the intestines?
ABC G5 and ABC G8
NB: these prevent the absorption of plant sterols
182
Where are bile acids reabsorbed?
terminal ileum
183
What happens when cholesterol arrives at the liver?
it down-regulates the activity of HMG CoA reductase
184
What does HMG CoA reductase do?
it is the main enzyme that is involved in the production of cholesterol from acetate and mevalonic acid
185
Where does the cholesterol in the liver come from?
1. produced by the liver
| 2. absorbed and transported to the liver (from the intestines)
186
What is the fate of cholesterol from the liver?
1. Hydroxylation by 7-alpha-hydroxylase into bile acids which will then be excreted by the via the bile ducts
2. Esterified by ACAT to produce cholesterol ester
- then, together with triglycerides and apoB, it is incorporated into VLDL particles
* * a transfer protein called MTP is very important in this packaging process**
187
What is the main precursor for LDLs?
VLDLs
188
What happens to LDLs in circulation?
they bind to LDL receptors on the surface of the liver and are taken up into the liver via endocytosis
189
What is the role of HDLs?
they pick up cholesterol from the periphery
190
Which transporter is important in packaging free cholesterol from the periphery into HDLs?
ABC A1
191
What is the role of CETP (cholesteryl ester transfer protein)?
it mediates the movement of:
* cholesterol from HDL to VLDL
* Triglyceride from VLDL to HDL
192
What is the role of SR-B1?
it is a receptor that takes HDLs into the liver
193
How do you get triglycerides from fatty foods?
fatty food hydrolysed ==> fatty acids; resynthestized ==> trigylcerides
194
How do triglycerides enter the plasma?
transported via chylomicrons
195
What happens to chylomicrons in the capillaries?
hydrolysed by lipoprotein lipase enzymes ==> free fatty acids
196
What tissues take up free fatty acids?
liver and adipose tissue
197
What happens to free fatty acids in the liver?
resynthesised into triglycerides and packaged into VLDLs
198
How do you liberate free fatty acids from VLDLs?
lipoprotein lipase
199
Dominant mutations of what genes cause familial hypercholesteraemia (type II)?
1. LDL receptor
2. ApoB
3. PCSK9
200
What is polygenic hypercholesterolaemia?
primary hypercholesterolaemia caused by multiple gene mutations including:
NPC1L1, HMGCR and CYP7A1 polymorphisms
201
What is hyperalphalipoproteinaemia?
deficiency of CETP ==> increase in HDL
202
What is phytosterolaemia?
disease in which plasma concentrations of plant sterols are increased, due to mutation in ABC G5 and ABC G8
**premature atherosclerosis is v common**
203
Clinical features of familial hypercholesterolaemia?
* FH of high cholesterol
* early onset hypercholesterolaemia
* corneal arcus
* xanthelasma
* tendon xanthomas
204
What causes Familial Type I Primary Hypertriglyceridaemia?
deficiencies in:
1. lipoprotein lipase (degrade chylomicrons)
2. ApoC II (lipoprotein lipase activator)
205
What causes Familial Type IV Primary Hypertriglyceridaemia?
increased synthesis of triglyceride
206
What causes Familial Type I Primary Hypertriglyceridaemia?
deficiency of ApoA V
207
What are the types of primary mixed hyperlipidaemia?
1. Familial combined hyperlipidaemia
2. Familial hepatic lipase deficiency
3. Familial dysbetalipoproteinaemia (type III)
208
What causes Familial dysbetalipoproteinaemia (type III)
aberrant form of ApoE [E2/2 instead of E3/3]
209
What is the diagnostic clinical feature of Familial dysbetalipoproteinaemia (type III)?
palmar stria (yellowing of the palmar crease)
210
What are the hormonal causes of secondary hyperlipidaemia?
* Pregnancy
* Exogenous sex hormones
* hypothyroidsim
211
What are the metabolic causes of secondary hyperlipidaemia?
* DM
* Gout
* Obesity
* Progressive partial lipodystrophy
* Storage disorders
212
What are the renal causes of secondary hyperlipidaemia?
* Nephrotic syndrome
the loss of protein in the urine and low serum albumin makes you switch on LDL synthesis
* Chronic renal failure, on dialysis and post-transplant
213
What are the hepatic causes of secondary hyperlipidaemia?
Obstructive liver disease
214
What are the toxic causes of secondary hyperlipidaemia?
* Alchohol
| * Diocin and chlorinated hydrocarbons
215
What are the iatrogenic causes of secondary hyperlipidaemia?
* Anti-HTN
* Immunosuppressants
* Other drugs
216
What happens in A, beta-lipoproteinaemia?
extremely low levels of cholesterol
due to MTP (microsomal triglyceride transfer protein) deficiency
217
What happens in hypobeta-lipoproteinaemia?
low LDL
caused by mutation in the ApoB gene leading to truncated versions of the protein
218
What happens in Tangier disease?
deficiency of HDL
caused by mutation of ABC A1
219
What causes hypoalpha-lipoproteinaemia?
mutation of ApoA1
220
How are foam cells formed?
LDL oxidised; taken up by macrophages; within macrophages, LDLs esterified ==> foam cells
221
What do statins do?
lower LDL cholesterol
+ small increase in HDL & triglycerides
222
What do fibrates do?
lower triglycerides
223
What is the function of Ezetimibe?
cholesterol absorption blocker (blocks NPC1L1)
224
What is the function of Colestyramine?
resin that binds to bile acids and reduces their absorption
225
What is the management of obesity?
1. hypocaloric diet and exercise
2. Iatrogenic malabsorption (Orlistat 120-360mg daily)
NB: this is a pancreatic lipase inhibitor
3. Bariatric surgery (if BMI >40)
226
What is the main SE of orlistat?
steatorrhoea
227
What are the types of bariatric surgery?
1. gastric banding
2. roux-en-Y gastric bypass
3. biliopancreatic diversion
228
What is a gastric band?
the size of the stomach is reduced using a band so that you feel full even after a small meal
229
What is a roux-en-Y gastric bypass?
the distal part of the jejunum is anastomosed to the stomach
230
What is biliopancreatic diversion?
a connection is made straight from the stomach to the terminal ileum + the stomach is reduced in size
231
What are the benefits of bariatric surgery?
* Reduces diabetes risk
* Reduces serum triglycerides
* Increases HDL levels
* Reduces fatty liver
* Reduces blood pressure
232
What are the risks of bariatric surgery?
* post operative mortality = 0.1 - 2%
233
How do we define success in bariatric surgery?
50% reduction in XS weight
when XS wt is defined as the difference between actual and ideal weight
234
Where is H+ excreted?
kidney
235
What are the buffers for H+
1. **bicarbonate**
2. Hb
3. Phosphate
also protein and bone
236
How does bicarbonate buffer H+ ?
H+ + HCO3- <==> H2CO3
ECF, Glomerular filtrate
237
How does Hb buffer H+?
H+ + Hb- <==> HHb
red cells
238
How does Phosphate buffer H+?
H+ + HPO4- <==> H2PO4
renal tubular fluid, intracellular
239
How is the buffer system maintained in the kidney?
H+ excreted, bicarbonated regenerated
240
How is bicarbonate regenerated?
from carbonic acid
241
How is H+ transported through the membrane in the kidneys?
Na+/H+ exchange via transporter
242
How is CO2 excreted?
via the lungs
243
How is respiration controlled?
chemoreceptors in the hypothalamic respiratory centre
increased CO2 = increased ventilation = increased CO2 clearance
244
What are some causes of metabolic acidosis?
1. increased H+ production
i. e. DKA
2. Decreased H+ excretion
i. e. renal tubular acidosis
3. Bicarbonate loss
e. g. intestinal fistula
245
What do you see on an ABG of metabolic acidosis?
increased H+ (low pH) with decreased bicarbonate
246
What do you see on an ABG of compensated metabolic acidosis?
1. increased H+ (low pH) with decreased bicarbonate = metabolic acidosis
2. low pCO2 (increased ventilation to compensate)
247
What do you see on an ABG of respiratory acidosis?
increased CO2 + increased H+ (low pH) + slight increase in bicarbonate
248
What are some causes of respiratory acidosis?
1. decreased ventilation
2. poor lung perfusion
3. impaired gas exchange i.e. COPD
249
What do you see on an ABG of compensated respiratory acidosis?
1. high pCO2, high bicarb
2. normal H+ (due to increase kidney excretion
NB: metabolic compensation much slower than respiratory
250
What are some causes of metabolic alkalosis?
1. H+ loss
2. Hypokalaemia
3. ingestion of bicarbonate
251
What do you see on an ABG of metabolic alkalosis?
increased H+ (high pH) with increased bicarbonate
252
Why does hypokalaemia cause alkalosis?
If you are hypokalaemic, you cannot excrete H+ ions.
253
What do you see in compensated metabolic alkalosis?
To compensate, the respiratory centre is inhibited leading to a rise in pCO2.
254
What are the causes of respiratory alkalosis?
Due to hyperventilation:
1. voluntary
2. artificial ventilation
3. stimulation of respiratory centre
255
What is the impact of prolonged respiratory alkalosis?
decreased renal H+ excretion
| + decreased bicarbonate excretion
256
How do you do an assessment of acid-base status?
1. H+/pH: acidosis or alkalosis
2. bicarbonate: metabolic?
2. pCO2: respiratory? compensation?
3. pO2: tissue function and oxygenation
257
In acid-base handling:
High CO2 leads to...?
respiratory acidosis
258
In acid-base handling:
Low CO2 leads to...
respiratory alkalosis
259
In acid-base handling:
high bicarb leads to...
metabolic alkalosis
260
In acid-base handling:
low bicarb leads to...
metabolic acidosis
261
What are the routes of pathogen entry into the CNS
1. **haemotogenous (e.g. pneumococcus, meningococcus)**
2. Direct implantation (e.g. trauma)
3. Local extension (e.g. from the ear)
4. PNS into the CNS (e.g. rabies*
262
What are the causes of aseptic meningitis?
1. enterovirus
2. herpes
NB: these also spread via haematogenous
263
What are the clinical features of meningitis?
* fever, headache, stiff neck
| * disturbance of brain function
264
What are the clinical features of encephalitis?
* disturbance of brain function
265
What are the clinical features of myelitis ?
* disturbance of nerve transmission
266
What are the clinical features of neurotoxicity?
* paralysis
= rigid (tetanus)
= flaccid (botulism
267
What is meningitis?
inflammation of the meninges and CSF
268
What is meningoencephalitis?
inflammation of the meninges and the brain parenchyma
269
How can meningitis cause neurological damage?
1. direct bacterial toxicity
2. Indirect inflammatory process and cytokine release and oedema
3. shock, seizures and cerebral hypoperfusion
270
What is the classification of meningitis?
* Acute (hours to days)
* Chronic (days to weeks
* Aseptic (viral so no pus)
271
Which organisms cause acute meningitis?
1. Neiserris meningitidis (A, B and C)
2. Streptococcus pneumoniae
3. Haemophilus influenzae
272
What N/ meningitidis serotype is given in the Meningitis vaccine?
C
You can pay for Men B
273
Which organism commonly causes meningoencephalitis?
Listeria monocytogenes
274
Which organism commonly causes neonatal meningitis?
Group B strep
275
Which organism commonly causes meningitis in old people and neonates?
Escherichia coli
276
Name some rare causative organisms for meningitis?
1. TB: caseating lesions on scan
2. S. aureus
3. T pallidum
4. Cryptoccus neoformans
277
What is the entry and transmission of N. meningitidis
transmission: person-to-person
entry: nasopharyngeal mucosa
278
What causes the clinical features of septicaemia?
1. capillary leak
= albumin and other plasma proteins lead to hypovolaemia
2. Coagulopathy
= bleeding and thrombosis; endothelial injury = platelet release reactions; the protein C pathway and plasma anticoagulants are affects
3. Metabolic derangement
= particularly acidosis
4. myocardial failure
+ multi-organ failure
279
What is the clinical profile of TB meningitis?
* fever, headache, neck stiffness
* takes weeks to present
* more common in immunosuppressed pts
* leptomeningeal enhancement
280
What are the complications of TB meningitis?
* tuberculous granulomas
* tuberculous abscesses
* cerebritis
281
What is the clinical profile of Aspetic meningitis?
* Presentation: headache, stiff neck, photophobia +/- non specific rash
* MOST COMMON Organisms:
- Coxsackie group B
- Echoviruses
* Usually occurs in children <1 year
**MOST COMMON infection of the CNS**
282
What is the most common mode of transmission in encephalitis?
nearly ALL haematogenous:
- person-to-person
- vectors (mosquitos, lice, ticks)
283
Which virus is becoming the leading cause of encephalitis worldwide?
West Nile VIrus
284
What are the vectors for West Nile Virus?
mosquitoes and birds
285
Which species is responsible for bacterial encephalitis?
listeria monocytogenes
286
Which species are responsible for amoebic encephalitis?
1. Naegleria fowleri
Habitat - warm water
2. Acanthamoeba species & Balamuthia mandrillaris
* Brain abcess, aseptic and chronic meningitis
NB: spread through direct extension (i.e. per cribiform plate)
287
What is the clinical profile of toxoplasmosis in encephalitis?
* obligate intracellular protozoal parasite: toxoplasma gonadii
* spread: oral, transplacental or organ transplant route
* causes SEVERE infection in immunocompromised pts
* affects organs including:
- grey and white matter of the brain
- retinas
- alveolar lining of lungs
- heart
- skeletal muscle
288
What is the most common route for brain abscesses?
direct extension
e.g. otitis media, mastoiditis, paranasal sinuses
NB: can occasionally spread haematogenously (e.g. endocarditis)
289
What are the causative organisms for brain abscesses?
* streptococci
* staphylococci
(NB: strep and staph are common ENT organisms)
* gram-negative organisms (mainly in neonates)
* TB
* Fungi
* Parasites
* Actinomyces and Nocordia species
290
What is the most common vertebral infection?
pyogenic vertebral osteomyelitis
usually caused by staph or steph
291
What can untreated pyogenic vertebral osteomyelitis lead to?
* permanent neurological deficits
* significant spinal deformity
* death
292
What are the risk factors for pyogenic vertebral osteomyelitis?
* age
* IVDU
* Long-term systemic steroids
* DM
* Organ transplantation
* Malnutrition
* Cancer
293
Which imaging modality is best for detecting parenchymal abnormalities (such as abscesses and infarctions)?
MRI
NB: CT scans more readily available
294
What are the investigations for meningitis?
1. Blood culture
2. Throat swab
3. Blood PCR
4. Sputum culture
5. Urine culture
295
What do you look for in CSF studies?
* colour/clarity
* cell counts
* chemistry (protein and glucose)
* stains (gram, auramine (TB), India ink (fungi)
* cultures
* with/without antigen screens
* PCR
296
What does a normal CSF result look like?
Appearance: clear
Cells: 0-5 leukocytes
Gram Stain/antigen tests: negative results
Protein: 0.15 - 0.4
Glucose: 2.2 - 3.3. 60% blood glucose level
297
What does a CSF result in purulent meningitis look like?
```
Appearance: turbid
Cells: 100-200 polymorphs
Gram Stain/antigen tests: Positive results
Protein: high
Glucose: low
Main DDx: Bacterial meningitis
```
298
What does a CSF result in aseptic meningitis look like?
Appearance: clear or slightly turbid
Cells: 15 - 500 lymphocytes
Gram Stain/antigen tests: Negative results
Protein: high
Glucose: normal
Main DDx: Viral meningitis, partially ABx treated bacterial meningitis, encephalitis, brain abscess, TB/fungal meningitis
299
What does a CSF result in TB meningitis look like?
Appearance: clear or slightly turbid
Cells: 30-500 lymphocytes or some polymorphs
Gram Stain/antigen tests: Negative results (scant acid fast bacilli)
Protein: v high
Glucose: low
Main DDx: TB meningitis, brain abscess, cryptococcal meningitis
300
Name the organism:
* gram-positive
* alpha-haemolytic
* diplococci
Streptococcus pneumoniae
301
Name the organism:
* gram-negative
* diplococci
* NO haemolysis
meningococcus
302
Name the organism:
* gram-positive
* rods
listeria monocytogenes
303
How does TB appear on a Ziehl-Neelsen stain?
Red and Blue
304
What are the pathogenomic features of cryptococcal meningitis?
* high opening pressure on LP
| * orbit structure (yeast in the middle, capsule on the outside) on INDIA INK stain
305
Who does cryptococcal meningitis usually effect?
Immunocompromised people (i.e. HIV)
306
What is the generic therapy for meningitis?
Ceftriaxone
| * if >50, immunocompromised: + amoxicillin (for listeria cover)
307
What is the generic therapy for meningo-encephalitis
Aciclovir + ceftriaxone
| * if >50, immunocompromised: + amoxicillin (for listeria cover)
308
Which organisms is ceftriaxone good at killing?
* meningococcus
* pneumococcus
* haemophilus
* E. coli
309
What Abx can you use to treat S.pneumoniae and N. meningitides in meningitis?
* Pencillin
* Ampicillin
* Ceftriaxone
* Chloro
310
What Abx can you use to treat H. influenzae in meningitis?
* Ceftriaxone
| * Cefotaxime
311
What Abx can you use to treat Group B Strep in meningitis?
* Pencillin [+ aminoglycoside]
| * Ampicillin
312
What Abx can you use to treat Listeria in meningitis?
* Ampicillin [+ aminoglycoside]
| * Pencillin
313
What Abx can you use to treat Gram negative bacilli in meningitis?
* Ceftriaxone
| * Cefotaxime
314
What Abx can you use to treat Pesudomonas in meningitis?
* Meropenem
| * Ceftazidime
315
What is in a portal triad?
hepatic artery, portal vein, bile duct
316
What is the Space of Disse?
spaces between the hepatocytes and the endothelium of the hepatocytes
this allows blood to come into contact with the liver enzymes
317
What is special about the arrangement of endothelial cells in the liver?
they are discontinuous
318
The area between the portal tract and the central vein is divided into how many zones?
3
Zone 1: closest to the portal tract so highest pO2
Zone 3: most susceptible to hypoxia; most metabolically active
319
What are the causes of high bilirubin?
* Pre-hepatic (unconjugated)
- haemolysis
- Gilbert's
Ix: FBC and blood film
* Hepatic
- Viral hepatitis
- Alcoholic hepatitis
- Cirrhosis
Ix: LFTs
* Post hepatic
- obstructive jaundice: gallstones, Ca head of pancreas
320
How do you measure fractions of bilirubin?
van den Bergh reaction
* A DIRECT reaction measures => CONJUGATED bilirubin
* the addition of METHANOL causes a complete reaction, to measure TOTAL BILIRUBIN
* TOTAL - CONJUGATED = UNCONJUGATED BILIRUBIN (indirect reaction)
321
What are the potential causes of neonatal jaundice?
**liver immaturity, leading to unconjugated hyperbilirubinaemia**
* hypothyroidism. Ix: TFTs
* haemolysis: Ix: Coombs test
322
What is the management of paediatric jaundice (pyschiological)?
Phototherapy
| Converts bilirubin ==> lumirubin + photobilirubin
these isomers do NOT need conjugation for excretion
323
What are the clinical features of Gilbert's syndrome?
* jaundice
* abnormal LFTs with NOS of liver pathology
* bilirubin worsened by fasting
324
What is the management of Gilbert's syndrome?
can manage conservatively OR
| give phenoarbital to reduce bilirubin levels
325
What is the pathophysiology of Gilbert's syndrome?
1. UDP glucoronyl transferase activity is reduced to 30%
2. Unconjugated bilirubin is tightly albumin bound and does not enter the urine
3. ==> no bilirubinuria
326
What form of bilirubin is always present in the urine of normal people?
Urobilinogen
327
Where does urobilinogen come from?
enterohepatic circularion
1. bilirubin travels through the biliary tree and into the bowel
2. bacteria in bowel convert bilirubin ==> stercobilinogen + urobilinogen.
3. urobilinogen is then reabsorbed into circulation and you pee it out
328
What is negative urobilinogen a sign of?
biliary obstruction
329
What is the most representative marker of liver function?
Prothrombin time
NB: normal PT 12-14s
NB: if PT (s) higher than no. of hours since overdose ==> liver unit for transplant
330
Which LFTs suggest intrahepatic damage?
ALT and AST
331
Which liver enzyme represents hepatic synthetic function?
Albumin
332
How do we measure liver function:
1. Clotting factors
2. Albumin
3. Bilirubin
333
What pathology causes high ALP?
post-hepatic (biliary obstruction)
334
How is Hep A transmitted?
faeco-oral route
335
What is the sequence of events after Hep A infection:
1. asymptomatic but infectious for a long time
2. viral titres begin to drop
3. IgM antibodies increase ==> unwell w/ jaundice
4. If you survive, IgG antibodies high ==> CURED
** no recurrence of Hep A**
336
What is the serology for active acute Hep B infection?
* HBsAg
| * HBeAg - highly infectious
337
What is the serology for previous Hep B infection
* anti-HBs
* anti-HBe
** anti-HBc CANT be measured**
338
What does the Hep B vaccine contain?
anti-HBsAg
339
What is the serology for chronic Hep B infection?
mounts an Ab response but never clears virus
1. HBeAg declines (highly infectious)
2. HBsAg remains
3. No Anti-HBs detectable (can detect Anti-HBc and Anti-HBe)
340
What colour does Mallory hyaline appear on Hematoxylin and eosin stain?
Pink
341
What is Mallory hyaline indicative of?
Alcoholic hepatitis
They are associated with fat deposit in the liver, which can be caused by alcohol. When hepatocytes are damaged by alcoholic hepatitis, you see ballon cells containing Mallory hyaline. NB: this may not be reversible.
342
What is collagen around individual liver cells characteristic of?
alcohol abus
343
What are the defining histological features of Alcoholic hepatitis?
* Liver cell Damage
* Inflammation
* Fibrosis
344
What are the associated histological features of Alcoholic hepatitis?
* fatty change
| * megamitochondria
345
What is the DDx for alcoholic hepatitis?
1. Non-alcoholic steatohepatitis
- looks exactly like alcoholic hepatitis
- most common cause of liver disease in Western worls
2. Alcoholic hepatitis
3. Malnourishment (kwashiorkor)
346
What is the management of alcoholic hepatitis?
1. Supportive
2. Stop alcohol
3. Nutrition (vitamins esp. thiamine: Pabrinex = B12 + thiamine)
4. Occasionally steroids
347
What is a common problem after alcoholic hepatitis
nodule development
This can make hepatic blood flow difficult leading to a rise in portal pressure) = intrahepatic shunting of blood
348
What vitamin is deficient in Beri-Beri?
B1
349
What are the features of Chronic stable liver disease?
* palmar erythema
* dupuytren's contracture
* mutliple spider naevi
* gynaecomastia
350
What is caput medusa and what causes it?
visible veins on the anterior abdominal wall due to portal hypertension
351
What are the clinical features of portal hypertension?
* visible veins (caput medusa)
* ascites
* splenomegaly
352
What is flapping tremor (asterixis) a clinical manifestation of?
hepatic encephalopathy
353
What is liver failure defined by:
1. failed synthetic function
2. failed clotting factor + albumin
3. failed clearance of bilirubin
4. failed clearance of ammonia (leads to encephalopathy)
354
What are the possible portosystemic anastomoses that arise for alcohol abuse?
1. Oesophageal varices
2. Rectal varices
3. Umbilical vein recanalising
4. Spleno-rectal shunt
355
What clinical sign is suggestive of obstructive jaundice?
scratch marks (due to itching)
the build up of bile acids and salts causes pruritis.
356
What is courvoisier's law?
if the gallbladder is palpable in a jaundiced patient, the cause is UNLIKELY to be gallstones
- more likely to be Ca head of pancreas
357
What does gallstones due to the gallbladder?
makes it small and fibrotic
358
What investigations do you do for post-hepatic jaundice?
1. Bloods (LFTs = high ALP)
| 2. USS abdomen
359
What is a common met for pancreatic cancer?
liver
the portal vein transports blood from cancer to liver
360
What are the types of inherited disorder?
1. Chromosomal
2. Polygenic (Medelian inheritance)
3. Monogenic (Medelian inheritance)
361
What are the potential outcomes of deficient enzyme activity?
1. Lack of end-product
2. Build up of precursors
3. Abnormal, often toxic metabolites
** These are the biochemical hallmarks of an inherited metabolic disorder**
362
What is the Inherited Metabolic Disorder (IMD) Screening Criteria (Wilson & Junger)
1. It has to be an important health problem
2. There must be an accepted treatment
3. Facilities for Dx and Tx
4. Latent or early symptomatic stage
5. Suitable test or examination
6. Test should be acceptable to the population
7. Natural history is understood
8. Agreed policy on whom to treat as pts
9. Economically balanced
10. Continuing process (keep updating what you are screening for)
363
What is biological markers of phenylketonuria (PKU) deficiency?
1. phenyalanin hydroxylase deficiency
- phenylalanine (essential amino acid) --> tyrosine
2. build up of phenylalanine in BLOOD
3. abnormal metabolites in URINE:
- phenylpyruvate
- phenyacetic acid
364
What is the Ix for PKU deficiency?
blood phenylalanine level
365
What is the management of PKU?
* monitor the diet: enough phenyalanine for life, not too much so toxic
** treatment has to be started WITHIN the first 6 wks of life or can lead to permanently low IQ**
366
What is sensitivity?
true positives / total number with the disease
367
What is specificity?
true negatives / total number without the disease
368
What is positive predictive value?
true positives / total number with positive result
NB: PPV is prioritised in screening for IMD because you do NOT want to miss a Dx
369
When is the Guthrie Test taken?
5-8 days of life?
370
What conditions are screened for on the Guthrie Test
1. PKU
2. Congenital hypothyroidism (high TSH)
3. Sickle cell disease
4. Cystic fibrosis
5. MCAD deficiency
Wales only:
6. Homocysteinuria
371
What is Medium-chain Acteyl-CoA Deficiency (MCAD) ?
fatty oxidation disorder => cannot break down medium chain fatty acids to small chain fatty acids in ketogenesis
fat used when fasting, or between meals to spare glucose stores. classic cause of cot death.
372
How do you screen for MCAD deficiency?
measure C6-C10 Acylcarnitines using tandem MS
373
What is the treatment for MCAD?
make sure the child never becomes hypoglycaemic (so they never become reliant on fats as source of energy)
374
What is a homocysteinuria?
failure of remethylation of homocysteine
375
What are the clinical features of homocysteinuria?
1. lens dislocation
2. mental retardation
3. thromboembolisation
376
What is the pathophysiology of Cystic Fibrosis?
1. failure of cystic fibrosis transmembrane conductance regulator (CFTR)
2. failure of Cl- to move from inside epithelial cells into the lumen
3. increased absorption of Na + and water =
** thick secretions** leading to ductal obstructions
377
What are the clinical features of CF?
1. Lungs
- recurrent infections
2. Pancreas
- malabsorption, steatorrhoea, diabetes
3. Liver
- cirrhosis
378
What is the screening test for CF?
immune reactive trypsinogen (IRT) = high!
379
How do you do the screening and Dx for CF:
1. If the IRT is above the 99.5th centile, go to ==> mutation detections
2. FOUR common mutations out of >500(F508 most common)
* 2/4 = CF Dx
* 1/4 = extend panel to 28
* 0/4 = repeat test @ 21 - 28 days
380
What is the key substrate in urea?
ammonia = HIGHLY TOXIC
381
Which is the typical mode of inheritance for urea cycle disorders?
autosomal recessive
= No FH
382
What is the mode of inheritance for ornithine transcarbamylase (OTC) deficiency?
X-linked
383
What is the key feature of urea cycle disorders?
Hyperammonaemia
384
What are the biochemical features of hyperammonaemia?
1. high glutamine (ammonia attaches to glutamate)
2. urine orotic acid high
3. amino acids with the urea cycle = high
385
What is the treatment for hyperammonaemia?
1. remove ammonia
* sodium benzoate
* sodium phenylacetate
* dialysis
2. reduce ammonia production (low protein diet)
386
What are the key clinical features of urea cycle disorders?
* vomiting without diarrhoea
* respiratory alkalosis
* hyperammonaemia
* neurological encephalopathy
* avoidance/change in dier
387
What are the biochemical features of organic aciduria?
hyperammonaemia with metabolic ACIDOSIS and high anion gap
388
What are the clinical features of organic aciduria in neonates?
* unusual odour (cheesy/smelly)
* lethargy
* feeding problems
* truncal hypotonia/limb hypertonia
* myoclonic jerks
** hyperammonaemia with metabolic ACIDOSIS and high anion gap (not lactate)**
Other: hypercalcaemia, neutropaenia, thrombocytopaenia, pancytopaenia
389
What are the clinical features of organic aciduria (chronic intermittent form)?
recurrent episodes of ketoacidotic coma
| cerebral abnormailties
390
What are the clinical features of Reye Syndrome?
* vomiting
* lethargy
* increased confusion
* seizures
* decerebration
* respiratory arrest
391
What are some of the triggers of Reye Syndrome?
* salicylates (aspirin)
* anti-emetics
* sodium valproate
392
What is included in a Reye Syndrome Metabolic Screen?
1. Plasma ammonia
2. Plasma/urine amino acid
3. Urine organic acid
4. Plasma glucose and lactate
* * NBL should be collected during acute episode**
**5. Blood spot carnitine profile (stays abnormal in remission) **
393
What is the biochemical profile of Mitochondrial Fatty Acid Beta-oxidation defects?
hypoketotic hypoglycaemia
394
What are the investigations for Mitochondrial Fatty Acid Beta-oxidation defects?
1. Blood ketones (low)
2. Urine organic acids (high)
3. Blood spot acylcarnitine profile (high)
395
What is the most severe and most common form of galactose metabolism?
Galactose-1-phosphate uridyl transferase (Gal-1-PUT)
396
What are the clinical features of Galactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency?
liver and kidney disease
features:
* vomiting
* diarrhoea
* CONJUGATED HYPERBILIRUBINAEMIA
* hepatomegaly
* hypoglycaemia
* sepsis (Gal-1-P inhibits immune response)
397
What happens when Galactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency is not picked up in infancy?
high Gal-1-PUT concentrations become substrate for aldolase (lens of eye) ==> bilateral cateracts
398
What are the Ix for Galactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency?
1. Urine reducing substances (high levels of galactose)
| 2. Red cell Gal-1-PUT
399
What is the treatment of Galactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency?
Avoid galactose (e.g. milk)
400
What is the pathophysiology of Glycogen Storage Disease Type I (von Gierke disease)?
Glucose-1-phosphate/Glucose-6-phosphate cannot be dephosphorylated so cannot be liberated from glycogen
= build up in liber and muscles
401
What are the clinical features of Glycogen Storage Disease Type I (von Gierke disease)?
* HYPOGLYCAEMIA
* hepatomegaly
* nephromegaly
* lactic acidosis
* neutropaenia
402
What is the consequence of defective ATP production?
multi-system disease esp. affecting organs with a high energy requirement (e.g. brain, muscles, kidney, retine, endocrine organs)
403
What is heteroplasmy of mitochondrial DNA?
once you reach a certain load of mitochondrial DNA, you start to develop symptoms
404
How is mitochondrial DNA inherited?
maternally
405
What Ix should you do for mitochondrial disorders?
1. High lactate (alanine)
- esp. after periods of fasting before and after meals
- Normal: lactate should be lower after fasting (opposite in mitochondrial disorder)
2. CSF lactate/pyruvate
3. CSF protein
- raise in Kearns-Sayre syndrome
4. CK
5. Muscle biopsy
- look for ragged red fibres
6. Mitochondrial DNA analysis
406
What is a congenital disorder of glycosylation?
defect of post-translational protein glycosylation
407
What are the clinical features of congenital disorders of glycosylation?
multi-system disorders associated with
- cardiomyopathy
- oesteopaenia
- hepatomegaly
sometimes: dysmoprhic facial and other features
408
Give an example of congenital disorder of glycosylation?
CDG type 1a
409
What are the clinical features of CDG type 1 a
* abnormal subcutaneous adipose tissue distribution with fat pads
* nipple retraction
410
What are common problems in LBW babies?
1. Respiratory Distress syndrome (RDS)
2. Retinopathy of prematurity (ROP)
3. Intraventricular haemorrhage (IVH)
4. Patent ductus arteriosis (PDA)
5. Necrotising enterocolitis
411
What are the clinical features of necrotising enterocolitis?
inflammation of the bowel wall progressing to necrosis and perforation
* bloody stools
* abdominal distension
* intramural air (pneumatosis intestinalis)
412
When is function maturity of glomerular function achieved?
2 years old
413
What are the differences in neonatal kidneys (when compared to adults)?
1. low GFR for their surface area
- slow excretion of solute load
- limited Na+ and H+ exchange
2. short proximal tubule = lower reabsorptive capacity:
- lower glycosuria threshold
3. reduced bicarbonate reaborption:
- propensity to acidosis
4. Loops of Henle and DCT are short and juxtaglomerular = reduced concentrating ability
5. DCT is unresponsive to aldosterone = persistent Na+ loss
- reduced K+ excretion
414
What happens to babies weight in their first week of life?
it goes down (due to fluid redistribution)
415
How much weight is safe for a baby to lose in the first week of life?
up to 10%
416
How do you manage sodium requirements in neonates born <30 weeks?
these babies have higher Na+ requirements, soL
* plasma Na+ measured DAILY
* K+ should only be given once urine output >1ml/kg/hr achieved
417
Why do premature neonates have high insensible water loss?
* high SA
* increased skin blood flow
* High RR and metabolic rate
* Increased transdermal fluid loss (skin not keratinised)
418
How do you manage electrolyte disturbance in neonates?
* bicarb for acidosis (NB: contains high Na+)
* Abx (usually sodium salts)
* caffeine/theophylline (for apnoea) - increase renal Na_ losses
* indomethacin (for PDA) - causes oliguria
* growth
419
What are the causes of hypernatraeimia in neonates?
* dehydration
- food-poisoning
- osmoregulatory dysfunction
NB: this is very UNCOMMON after 2 weeks of age
420
What causes congenital adrenal hyperplasia (CAH)?
deficiency of 21-hydroxylase
= reduced cortisol and aldsterone
= salt loss
the lack of 21-hydroxylase leads to an accumulation of 17-OH progesterone and 17-OH pegnenolone = high levels of androgens
421
What are the clinical features of congenital adrenal hyperplasia (CAH)?
* hyponatraemia/hyperkalaemia w/ volume depletion
* Hypoglycaemia (due to lack of cortisol)
* ambiguous genitalia in female neonates
NB: in males, this is not as obvious. may present as a salt-losing crisis.
* growth acceleration
422
What are the causes of hyperbilirubinaemia in a neonate?
1. high levels of bilirubin synthesis
2. low rate of transport into the liver
3. enhanced enterohepatic circulation
**NB: the bilirubin is UNCONJUGATED**
423
How much bilirubin can albumin bind?
1g/L of albumin binds 10micromol/L of bilirubin
average albumin @ term = 34g/L ==> binds 340micromol/L bilrubin
**NB: lower in prematurity***
424
What are the causes of hyperbilirubinaemia in a neonate?
1. haemolysis (ABO, rhesus)
2. G6PD deficiency
3. Grigler-Najjar syndrome
425
What is the definition of prolonged jaundice in neonates?
> 14 days in term
| > 21 days in premature babies
426
What are the causes of prolonged jaundice in neonates?
* prenatal infection/sepsis/hepatitis
* hypothyroidism
* breast milk jaundince
427
What is the definition of conjugated hyperbilirubinaemia?
> 20micromol/L
***NB: ALWAYS pathological***
428
What are the causes of conjugated hyperbilirubinaemia?
1. Biliary atresia (MOST COMMON)
- 20% associated w/ cardiac malformations, polysplenia, situs inversus
- early surgery is essential (<6 months)
2. Choledochal cyst
3. Ascending cholangitis in TPN
- lipids in the TPN seems to cause AC
4. Inherited metabolic diseases
- Galactosaemia
- alpha-1-AT
- tyrosinaemia
- Peroxisomal dis
429
What are the clinical features of Osteopaenia of prematurity?
fraying, splaying and cupping of long bones
* Calcium is usually NORMAL
* Phosphate is < 1mmol/L
* ALP > 1200U/L (10x adult ULN)
* Vitamin D - rarely measured)
430
What is the management of Osteopaenia of prematurity?
1. Phosphate/calcium supplements
| 2. 1-alpha calcidol
431
What is rickets?
osteopaenia due to deficient activity of Vitamin D
432
What is the presentation of rickets?
* frontal bossing
* bowlegs/ knock knees
* muscular hypotonia
* tetany/ hypocalcaemic seizure
* hypocalcaemic cardiomyopathy
433
What are the genetic causes of rickets?
1. pseudo-vitamin D deficiency I (defective renal hydroxylation)
2. pseudo-vitamin D deficiency II (receptor defect)
** 1 & 2 treated with 1, 25 OH Vitamin D**
3. Familial hypophosphataemias
- low tubular maximum reabsorption of phosphate
- raised urine phosphoethanolamine
434
Primary malignant bone tumours are more common in children or adults?
children
435
What is the site predilection for neoplastic bone disease?
knee
436
What is the typical presentation for neoplastic bone disease?
* pain
* swelling
* deformity
* fracture
437
What should you consider in the history of neoplastic bone disease?
1. Age
2. Site (different tumours = different site predilitcions)
3. Duration
4. History of trauma
5. Multiple lesions
6. Associated disease
438
What is the first step if you suspect a primary bone tumour?
X-ray
1. Evaluate the site, size and margin of the lesion?
2. Solitary/multiple lesions?
3. Does it extend into the soft tissue?
4. Associated disease or fracture?
439
What do you do if you suspect a primary bone tumour?
refer the pt urgently to a specialist centre
440
How do you Dx a bone tumour?
needle biopsy
* performed by a radiologist w/ a Jamshidi needle
* under US or CT guidance
NB: open biopsy may be used for inaccessible or sclerotic lesions.
**imprint (cytology) preparations are very useful**
441
What are the DDx for tumour-like conditions?
1. Fibrous dysplasia
2. Metaphyseal fibrous cortical defect/non-ossifying fibroma
3. Reparative giant cell granuloma
4. Ossifying fibroma
5. Simple bone cyst
442
What sites are most common for fibrous dysplasia?
ribs and proximal femur
443
What is the X-ray appearance of fibrous dysplasia?
'soap bubble' osteolysis
444
What problems are McCune Albright Syndrome associated with?
polyostotic disease associated with:
* endocrine problems
* cafe au lait spots
445
What is the histology of fibrous dysplasia?
marrow is replaced by fibrous stroma w/ rounded trabecular bone
446
What is the classification of benign cartilaginous bone tumours?
* osteochondroma
* enchondroma
* chondroblastoma
447
What is the classification of the benign bone-forming tumours?
* osteoid osteoma
* osteoblastoma
* osteoma
448
What is the typical profile of osteochondroma?
* ends of long bones
* male
* 10-20 years
449
What is an osteochondroma?
cartiliginous surface overlying the normal trabecular bone
450
What is an enchondroma?
cartilaginous proliferation within bone
451
What is the typical profile of enchondroma?
* Hands (w/ some in the feet)
X-RAY:
* pathological fractures
* popcorn calcification
Histology:
well circumscribed proliferation of cartilage
