Pathology Flashcards
Are fungi eukaryotic or prokaryotic?
Eukaryotic
Do fungi plasma membranes contain ergosterol?
Yes
What is the commonest cause of fungal infections in humans?
Candida spp.
What do we use to treat oral thrush?
Nystatin
What do we use to treat vulvovaginitis?
Co-trimazole (topical)
fluconazole (oral)
What is fluconazole used to treat?
Vulvovaginitis and oesophagitis.
Anidulafungin is an example of which drug class?
Echinocandin
C. Neoformans and C. Gatti are examples of organisms which cause which fungi?
Cryptococcus (a type of yeast).
Which animal is cryptococcus associated with?
Pigeons
Which variant of cryptococcus can cause Meningitis?
C. Gatti
What type of ink is used for a cryptococcal stain?
India = stains the CSF.
Which microorganism causes mycotoxicosis?
Aspergillosis (mould)
Name one fungi which actually lacks ergosterol in the cell wall.
Pneumocystis Jiroveci
What is a main risk factor for any fungi infection?
Immunosuppressed.
What is a dermatophyte?
A group of fungi characterised by the site they invade. e.g. tinea capitis. Invade the dead keratin of skin, nails, hair. LOVE DEAD KERATIN.
Tinea cruris’ target site is:
Groin
Tinea capitis target site is:
Scalp (cap)
Tinea corporis target site is:
Abdomen
Tinea pedis target site is:
Foot
Tinea pedis, capitis, corporis, crusis are examples of what?
Dermatophytes = examples of mould.
Pityriasis versicolor is caused by which fungi?
Malassezia furfur
What is the mechanism of azoles?
Inhibits the conversion of lanosterol - ergosterol by inhibiting cytochrome P450 enzyme: 14a demethylase.
SOB, cough in the history should point toward which fungal diagnosis?
Cryptococcus (associated with pigeons)
Which fungal infection can cause meningitis?
Cryptococcus
Give 5 risk factors for fungal disease:
Immunosuppressed Inhaled steroids malignancy Moisture (dermatophytes) Long lines (candida)
What does immunophenotype refer to?
Flow cytometry, immunohistochemistry
What does cytogenetics refer to?
FISH
Which is more common - Hodgkin’s lymphoma or non-hodgkin’s lymphoma?
Non Hodgkin’s Lymphoma.
Which is the characteristic cell on blood film in Hodgkin’s lymphoma?
Reed Sternberg cells
How do you diagnose Hodgkin’s lymphoma?
CT, PET, Blood tests, LDH, lumbar puncture
Name the 3 B symptoms
Fever, night sweats, weight loss.
Which is the most common type of Hodgkin’s lymphoma?
Nodular Sclerosing.
What does the cancer stage II describe?
> 1 group of nodes above the same side of the diaphragm.
What does the cancer stage I describe?
Only one group of nodes involved
What does the cancer stage III describe?
Nodes above and below the diaphragm involved
What does the cancer stage IV describe?
Extra nodal spread.
How do we treat Hodgkin’s lymphoma?
ABVD - Adriamycin Bleomycin Vinblastine Dacarbazine
+chemotherapy!
Which is the fastest growing type of Non-Hodgkin’s lymphoma?
Burkitt’s lymphoma
What does indolent mean?
Long term survival
i.e. less aggressive.
(paradoxically, more aggressive respond better to treatment).
Which is the lowest grade form of Non-Hodgkin’s lymphoma?
Follicular lymphoma
MZL - marginal zone lymphoma.
What is characteristic to see on blood film of chronic lymphocytic leukaemia?
Lymphocytosis
Smear cells
Which markers are seen in a normal B cell?
CD3-
CD5-
CD19+
Which markers are seen in a normal T cell?
CD3+
CD5+
CD19-
Which markers are seen in a malignant B cell?
CD3-
CD5+
CD19+
Where is Venetoclax used and how does it work?
Used in CLL - chronic lymphocytic leukaemia
Blocks the BCL2 protein.
Which is the most common malignant type of cancer?
Invasive ductal carcinoma
Which is the single most important prognostic factor for cancer?
Status of the axillary nodes i.e. is there metastasis?
Why are basal-like carcinomas so hard to treat with medication?
They are oestrogen/progesterone and HER2 negative.
Which are the three factors we look at in histological grading?
- Tubule formation
- Nuclear pleomorphism
- Mitotic activity
What is the purpose of NHS Breast screening programmes?
To screen for DCIS (ductal carcinoma in situ).
What would DCIS grade on a biopsy grade?
B5a
B5b = invasive carcinoma Grading = B1-B5. B1 = normal breast tissue, B2 = benign.
Which grade is benign tissue on biopsy?
B2! B1 = normal tissue.
How do we investigate breast disease?
Examination
Investigation: mammography, sonography
Pathology: cytopathology, histopathology
How are aspirates coded? What do these codes mean?
C1-C5
C1 = inadequate
C2 = benign
C5 = malignant
How is ‘benign’ coded on the cytology grading?
C2! C1 = normal tissue (inadequate) .
Define menarche
First occurrence of menstruation
Define fibroadenoma.
Benign fibroepithelial neoplasm of the breast.
Name x3 benign breast conditions.
Duct ectasia, mastitis, fat necrosis, papilloma
How would duct ectasia present in a patient?
And on microscopy?
Nipple discharge, breast tenderness.
Dilated ducts on microscopy
‘Painful, red breast’ points toward which diagnosis?
Acute mastitis.
Presentation with breast mass and can be confused for cancer. What is the diagnosis?
Fat necrosis
What is a papilloma?
Benign outward growth.
‘Benign neoplasm of the breast’ defines what?
Fibroadenoma
What is a Phyllodes tumour?
Benign but more aggressive fibroepithelial neoplasms.
Which are the receptors we assess when querying breast cancer?
Oestrogen receptor, progesterone receptor, HER2 receptor.
How will low grade tumours present receptor wise?
Oestrogen and progesterone receptor positive, HER2 receptor negative.
How will high grade tumours present receptor wise?
Oestrogen and progesterone receptor negative, HER2 receptor positive.
Tamoxifen targets which receptors?
oestrogen receptor.
Herceptin targets which receptor?
HER2 receptor.
Which are the vaccinations required at 8 weeks of age.
Diptheria Tetanus Pertussis Polio HiB (haemophilus influenzae) type B Hepatitis B
Name the three major pathogens at surgical site infections
Staphylococcus aureus
Pseudomonas aeruginosa
E.Coli
Give three things which increase an individual’s risk of surgical site infection.
- ASA score>3
- Diabetes - associated with post operative hyperglycaemia
- Malnutrition
- Low Albumin
- Rheumatoid arthritis
Why does obesity place someone at risk of surgical site infection?
Adipose tissue is poorly vascularised = poor oxygenation of tissues.
How does smoking increase risk of surgical site infection?
Nicotine prevents wound healing
Nicotine has vasoconstrictive effects.
Name the disinfectant/ antiseptic used on a patient’s skin pre-operatively.
Chlorhexidine.
What is the most powerful independent risk factor for SSI following cardiothoracic surgery?
Staphylococcus aureus
How does hypothermia cause increased risk of surgical site infection?
Hypothermia causes vasoconstriction = reduces oxygen and blood supply to wound.
Organisms adhering to the synovial membrane and bacteria growing in the synovial fluid causing inflammation. What is the diagnosis?
Septic arthritis
Name the three most important investigations for septic arthritis.
Blood cultures Synovial fluid aspiration ESR, CRP X ray; soft tissue damage US confirms effusion CT for erosive bone change
synovial count > 50, 000 cells/mm suggests septic arthritis. but negative does not exclude.
How do we manage septic arthritis?
Antibiotics e.g. cephalosporin, flucloxacillin.
Name three components of blood
Red cells
Platelets
FFP (fresh frozen plasma)
Cryoprecipitate
Which blood group do we give in an emergency?
Blood Group O negative
How are red cells stored compared with platelets?
Red cells = 4 degrees
Platelets = 20 degrees
Name a procedure which will most likely require a large amount of blood transfusion.
Aortic aneurysm repair
What is the difference between O positive and O negative blood?
O positive has RhD antigens
O negative does not have RhD antigens
Which are the two blood systems we are most concerned with with blood donation?
ABO and Rh.
If you are RhD negative and given RhD positive blood what is likely to happen?
You will make anti-D antibodies.
Do anti-D antibodies cross the placenta?
Yes because they are IgG antibodies.
Which blood group do we give in an emergency?
O negative
Where is giving platelets contraindicated?
TTP - thrombotic thrombocytopenic purpura.
How much FFP do we give?
15-20ml/kg.
Approximately how many ml makes up a unit?
450mL. (will vary between red cells, fresh frozen plasma and cryoprecipitate for example).
What is cryoprecipitate made up of?
Fibrinogen, fibronectin and factor VIII and vWF.
Which blood component mainly raises the levels of fibrinogen?
Cryoprecipitate.
Name the four main components of blood.
Red cells
Cryoprecipitate
Platetlets
Fresh frozen plasma
Name the two types of donor.
Allogeneic
Autologous
If someone is immunocompromised/ at risk of graft vs. host disease, which specific requirement of blood may they need?
Irradiated blood.
Which is actually the most frequency blood donor group?
O positive
Which blood groups are cross matched?
Red cells (not platelets/ FFP).
What do we worry about in RhD negative women?
HDFN - haemolytic disease of the foetus newborn.
Is haemolytic disease an acute or delayed reaction?
Delayed (i.e. >24 hours).
What is TACO?
Transfusion associated circulatory overload.
Name x3 ‘SHOTs’
Serious hazards of transfusion:
- Anti-D Immunoglobulin errors
- Delayed transfuion
- Avoidable transfusion
With which blood component transfusion are allergic reactions most common?
With plasma.
With which blood component transfusion are allergic reactions most common?
With plasma.
What is IgA deficiency?
A very severe allergic reaction; in 25% of patients, the person develops IgA antibodies in response to exposure to IgA e.g. in a transfusion.
Which is the most common pulmonary complication in blood transfusions?
TACO - Transfusion associated circulatory overload.
When may a delayed haemolytic transfusion reaction occur?
If blood transfused has the same antigens on the patient’s RBCs, the antibodies can cause RBC destruction.
after 3-10 days; delayed.
When may a delayed haemolytic transfusion reaction occur?
If blood transfused has the same antigens on the RBCs, the antibodies can cause RBC destruction.
How do we test for delayed haemolytic disease?
High bilirubin, high LDH
Low Hb.
How does GvHD occur?
Lymphocytes from the donor’s blood are not destroyed in the patient (e.g. in very immunocompromised patients) and so, the donor’s lymphocytes see HLA in the patient and attack them.
Name the top 3 symptoms in GvHD.
Diarrhoea
Liver failure
(always fatal).
Would purpura occur due to low or high platelet count?
Low platelet count = insufficient clotting = bleeding to surface of skin.
Why may iron overload occur and at what levels?
After multiple transfusions of blood = iron build up if not excreted. Prevent by iron chelation once ferritin > 1000. = chelating agents to remove iron. ‘Deferasirox’
Which antibodies can cross the placenta?
Only IgG.
How can haemolytic disease of the newborn occur?
Maternal antibodies cross the placenta and destroys fetal red cells.
How does giving anti-D immunoglobulin prophylactically work?
72 hours within an event e.g. bleed, give red cells coated in anti-D Ig (immunoglobulin) = mother’s spleen will remove them before body has time to develop antibodies to anti-D (sensitisation will not occur).
- does not work if mother already has anti-D antibodies
- we give anti-D antibodies at delivery if feotus is already known to be RhD Positive.
How does giving anti-D immunoglobulin prophylactically work?
72 hours within an event e.g. bleed, give red cells coated in anti-D Ig (immunoglobulin) = mother’s spleen will remove them before body has time to develop antibodies to anti-D.
What are the doses of anti-D that we give before and after 20 weeks of pregnancy?
Before 20 weeks = 250 iu
After 20 weeks = 500 iu
What is sensitisation?
In effect to produce an allergic response - to cause antigens to bind to antibodies.
What is HLA?
a complex of genes (MHC) on chromosome 6 - proteins found on cells e.g. MHC class II found on CD8+ T cells.
What is HLA?
a MHC on chromosome 6 - proteins found on cells e.g. MHC class II found on CD8+ T cells.
Which chromosome is HLA found on?
Chromosome 6.
Which HLA Class is expressed on all cells?
HLA Class I (A, B, C)
HLA Class III is DQ, DR, DP.
HLA is found on which cells?
The APC (HLA is a MHC found on the APC to present to the T cell).
How can HLA be a problem in transplantation?
HLA genes are so variable between human beings = creates mismatches in transplantation due to immune reactions as ‘foreign material’.
e.g. = donor is HLA-A1 when recipient has a mix of HLA-A 1 and HLA-A2
Are anti-HLA antibodies naturally occuring?
No; they are formed later in life e.g. during pregnancy or transplantation (after a stimulation).
Not like anti-A or anti-B.
Are anti-A and anti-B antibodies naturally occuring?
Yes.
Name two ways in which we can prevent graft rejection?
ABO/ HLA tissue matching
Anti-HLA antibody screening
Name two ways in which we can prevent graft rejection?
ABO/ HLA tissue matching
HLA screening
Which are the three infections currently screened for during pregnancy?
HIV
Hepatitis B
Syphilis
What is the TORCH screen?
Used for screening congenital infections; Toxiplasmosis Other (HIV, hepatitis B syphilis) Rubella Cytomegalovirus HSV.
Name 3 typical signs in congenital infection.
Rashes
Jaundice
Hepatosplenomegaly
Name three clinical features of congenital rubella syndrome?
Eyes - cataracts, glaucoma
Ears - deafness
Heart - PDA, ASD/VSD.
Name three clinical features of congenital rubella syndrome?
Eyes - cataracts, glaucoma
Ears - deafness
Heart - PDA, VSD.
How does the treatment differ in early onset sepsis Vs. late onset sepsis?
Early onset antibiotics: Benzylpenicillin +gentamycin
Late onset antibiotics = cefotaxime + vancomycin.
Which is the most important bacterial cause of paediatric mortality and morbidity?
Meningitis
Name 3 investigations for meningitis
Lumbar puncture for CSF.
Throat swabs
Blood cultures
How does viral fluid appear on CSF?
Clear Normal glucose (bacterial = low glucose).
How does viral fluid appear on CSF?
Clear
Which is the most important microorganism cause of paediatric mortality and morbidity?
Streptococcus pneumoniae.
Which are the two main species responsible for Meningitis?
Neisseria Meningitidis
Streptococcus pneumoniae.
Are most respiratory infections in children bacterial or viral?
Viral
What is the most bacterial cause of respiratory tract infections in children?
Streptococcus pneumoniae.
Which treatments are commonly the treatment of choice in children with bacterial respiratory tract infections?
Macrolides e.g. azithromycin; many strains are resistant to penicillin or amoxicillin.
Bordetella pertussis is responsible for which condition?
Whooping cough.
Which is the biggest culprit for Urinary tract infections?
E.Coli
What is the relationship between GFR and clearance?
GFR and clearance should equal one another if markers are not reabsorbed/ filtered or bound to serum proteins.
Which is the gold standard marker to measure GFR?
Inulin (collected from urine)
What is inulin?
The perfect Gold standard marker to measure GFR.
However, not suitable to adminster
so use Cr-EDTA.
Name three characteristics of the ideal marker to measure GFR.
Not reabsorbed
Freely filtered at glomerulus!
Not plasma protein bound.
What is the disadvantage of using urea as a marker for GFR?
Urea is reabsorbed by the tubular cells.
What is the disadvantage of using creatinine as a marker for GFR?
Actively secreted into the urine by tubular cells.
Related to muscle mass.
Is Creatinine the ideal marker for measuring GFR?
No. can be used but actively secreted by the tubular cells into the urine.
Is the issue with creatinine that it is reabsorbed by the tubular cells?
No; it is actively secreted by tubular cells.
Urea is reabsorbed by tubular cells.
The Cockcroft Gault equation can be used to measure what more accurately?
Creatinine clearance.
Incorporates weight and gender
What is Cystatin?
A marker of GFR (again, not the best as reabsorbed. Inulin = ideal).
For creatinine clearance, can we take a single urine sample?
No; needs a 24hour collection sample.
The Bence Jones protein in urine is diagnostic for which condition?
Multiple myeloma (blood cancer affecting plasma cells).
Does the urine dipstick test sensitively detect bence jones proteins?
No. Usual urine dipstick testing is not sensitive to BJPs.
You can reliably exclude bacteriuria if the urine
dipstick is negative for nitrites. True or false.
True.
What does urine microscopy examine for?
Crystals, red blood cells, white blood cells.
Centrifuge at 3000rpm.
Calcium oxalate crystals and alcoholic poisoning. What is the likely diagnosis?
Ethylene glycol poisoning.
Which white blood cell is bilobar?
Eosinophil
What is the best way to measure kidney function?
GFR not creatinine.
best way to measure GFR is through inulin (but not always realistic).
How many stages in acute kidney injury?
3 stages.
AKI Stage 1 (more than x1.5-1.9 fold creatinine)
AKI Stage 2
AKI Stage 3 (more than 3 fold baseline creatinine)
Pre renal kidney injury is associated with structural abnormalities. True or false?
False = why pre renal injury responds to restoration of volume.
What is the difference between pre-renal acute kidney injury and acute tubular necrosis?
Pre renal AKI responses to restoring circulatory volume (i.e. fluids) due to there not being structural damage whereas acute tubular necrosis does not.
A 68 year old man with previously normal renal function is found to have a creatinine of 624μmol/l. What is the likely cause of his AKI?
Benign prostatic hyperplasia.
Acute blood loss is likely to cause which kind of kidney injury?
Pre-renal acute kidney injury
Obstructive uropathy is likely to cause which kind of AKI?
Post-renal acute kidney injury.
Vasculitis and glomerulonephritis are likely to cause which kind of acute kidney injury?
Intrinsic AKI.
What is rhabdomyolysis?
Breakdown of muscle releasing leaked muscle content into the circulation.
What are the four stages of wound healing?
Haemostasis
Inflammation
Proliferation
Remodelling
How many stages of chronic kidney disease are there compared with acute kidney disease?
Acute = 3 stages Chronic = 5 stages
What is the main marker for chronic kidney disease?
ACR - albumin: creatinine ratio.
Name three consequences of Chronic kidney disease.
Hyperkalaemia Acidosis Anaemia Renal bone disease Hyperparathyroidism Uraemia
Acidosis and hyperkalaemia are main causes of which kidney disease?
Chronic kidney disease.
Does kidney failure result in acidosis or alkalosis?
Acidosis; failure of kidney to excrete protons.
How do we treat acidosis?
Sodium bicarbonate.
What two measures do
we use to define acute kidney injury?
Creatinine and urine output.
Which medications can cause hyperkalaemia?
potassium sparing diuretics e.g. spironolactone
ACE Inhibitors
How does chronic renal disease cause anaemia?
Decline in erythropoietin producing cells.
Usually normocytic, normochromic.
What is an ESA?
Erythropoietin stimulating agent.
How can chronic kidney disease (CKD) cause hyperparathyroidism?
High PTH causes low Vitamin D and high phosphate = resistance to PTH = hypocalcaemia = high PTH
What is 1-alpha calcidol
Vitamin D receptor activator.
What cardiovascular impact can chronic kidney disease have?
Uraemia
= uraemic cardiomyopathy.
BMI >30 is a contraindication to transplantation. True or false?
False.
What is the difference between haemodialysis and peritoneal dialysis?
Haemodialysis = Artery to machine outside of the body which acts as a filter.
Peritoneal dialysis = Lining of the belly acts as a natural filter.
What is usually the route of administration for adrenaline in anaphylaxis?
Intramuscular; intravenous is used rarely e.g. in cardiac arrest.
What is the typical dose of adrenaline for children aged 6-11 years in anaphylaxis?
300 micrograms of 1:1000 adrenaline IM. Repeat every 5 minutes if necessary.
How often is adrenaline repeated in anaphylaxis?
Every 5 minutes.
Which is the most appropriate test for food allergies?
Skin prick test.
What is the amount of adrenaline injection in children Vs adults?
Children = 300mcg Adults = 500mcg.
Give three signs of anaphylaxis.
Urticarial rash
Stridor
Acute onset hypotension
Respiratory distress
What is chlorphenamine?
An antihistamine
Which is the test we use most commonly to test for contact dermatitis?
Skin patch test.
What is the best enzyme to confirm anaphylaxis?
Tryptase levels (remains elevated for 12 hours following episode).
On examination a patient has gross facial and tongue oedema - should they be treated for anaphylaxis IM or IV?
IM still. IV for severe reactions e.g. shock
What is the typical dose of adrenaline for children aged 6 months - 5 years in anaphylaxis?
150 micrograms (1 in 1000)
What is refractory anaphylaxis?
Respiratory and cardiovascular problems.
What does HAI stand for?
Healthcare associated infection. (not hospital acquired!)
Antibiotic associated diarrhoea is most likely caused by which organism?
Clostridium difficile.
Give two examples of E.Coli associated infection
Urinary catheter (UTI)s Ventilator associated (pneumonia)
How prevalent are HAI in the UK?
300 000 a year -
Which is the most common HCAI?
Clostridium difficile
What kind of bacteria is Clostridium difficile?
Gram positive spore forming anaerobe.
What kind of bacteria is Clostridium difficile?
Gram positive spore forming anaerobe.
Produces toxins A and B.
Name one key risk factor Clostridium difficile infection.
Antibiotic use.
Which is the first line treatment for Clostridium difficile?
Vancomycin/ Fidaxomicin
Which is the main bacteria associated with catheter infection?
E.Coli
Name some commonly resistant gram negative bacteria.
E. Coli, klebsiella, enterobacter
Which bacteria has high resistance to antibiotics?
Enterobacter
Which is the go to antibiotic for cellulitis?
Cefuroxime and Vancomycin
For MRSA, which is the go to antibiotic?
Meropenem and Vancomycin
For MRSA, which is the go to antibiotic?
Meropenem and vancomycin
Name three places where MRSA may be found in HAI?
Catheters, UTI associated catheters, SSI.
Give some examples of how we can class immune deficiencies.
Metabolic Infection Age Malnutrition Environmental Drug
What is the commonest cause of secondary immune deficiencies?
Malnutrition.
How would you classify methotrexate?
Cytotoxic agent
What type of drug if phenytoin?
Anti epileptic
Which biological agent is associated with reactivation of TB?
Anti-TNF agents.
Name three haematological cancers (blood cancers)
Multiple Myeloma
Non Hodgkin’s lymphoma
CLL - Chronic lymphocytic leukaemia
What is FISH?
FBC
Immunoglobulins (IgG, IgA, IgM, IgE).
Serum complement (C3, C4)
HIV test
What is the main method by which serum protein electrophoresis works?
SPE separation through charge.
Where can SPE be helpful?
Serum protein electrophoresis: can detect monoclonal bands seen in blood cancers e.g. multiple myeloma, NHL.
SPE can miss 20% light chains.
What can SPE miss?
Identifying light chains.
What type of vaccine is the Tetanus vaccine?
Protein antigen.
What type of vaccine is the Pneumovax?
Carbohydrate antigen
What is key diagnostic aspect for primary antibody syndromes?
Failure to respond to vaccination.
Flow cytometry is mainly used to assess which cell type?
The lymphocyte
Name the three tests we should do for immune deficiencies.
FISH, renal and liver profile, calcium and bone profile, SPE (serum protein electrophoresis) and flow cytometry, assessment of IgG classes.
Which are the four incurable sexually transmitted diseases?
HIV
Hepatitis B
Herpes
HPV
What is the pathogenesis of HIV?
HIV virus binds to CD4 then CCR5 and CXCR4
Replicates via a DNA intermediate
Which is the bacterium associated with reheated cooked rice?
Bacillus cereus.
How would campylobacter jejuni present in a patient?
BLOODY diarrhoea and vomiting.
Which is the first line medication of choice for a patient presentation of bloody diarrhoea and vomiting?
Ciprofloxacin.
Which medication is usually used for traveller’s diarrhoea?
Clarithromycin.
Which is the most common cause of Traveller’s diarrhoea?
E. Coli.
Which is the most common cause of Traveller’s diarrhoea with a 15 day long history?
Giardiasis.
Low Hb and low reticulocyte count is likely to point toward which diagnosis?
Parvovirus B19 infection due to aplasia in this infection.
Vaginal WHITE discharge with fishy smell points toward which diagnosis?
Bacterial vaginosis.
What is the key organism causing bacterial vaginosis?
Gardnerella vaginalis.
How does bacterial vaginosis compare with trichomonas?
Bacterial vaginosis = white discharge
Trichomonas = green, frothy discharge.
What is the medical term for the bull’s eye rash and in which condition is it seen?
Erythema Migrans - seen in Lyme’s disease.
Which test should be offered to all those with TB?
A HIV test; TB is an ‘AIDS defining’ illness.
Which is the most common cause of pyelonephritis?
E.Coli
Which bacteria is typically due to the cause of diarrhoea following rice?
Bacillus cereus.
What is an aspergilloma?
A mass caused by the fungus aspergillus which is associated with TB.
What happens to CD4+ T cells in chronic HIV?
CD4+ T cell depletion
Impaired CD4+ and CD8+ T cells
In acute HIV, some increase in CD8+
How do we diagnose HIV infection?
‘4th Generation testing’
HIV antigen and antibody testing.
Assays detect specific antigens.
Name three comorbidities of HIV.
TB Diabetes Mellitus GORD Hepatitis B and C Depression and anxiety
Name three baseline investigations for HIV.
Full Blood count
Renal, liver and bone profile
Sexual health screen
Baseline chest x ray and ECG.
Name three things which determine the magnitude of the HIV viral load on a graph.
CD8+ count
Immune activation
Genetics
Viral genetics
Name one key virus where CD4+ is the lowest.
CMV
Cytomegalovirus.
Which is the most important prognostic indicator in HIV patients?
CD4+ T cell count
Ritonavir works through which mechanism and for which condition?
Protease inhibitor
In HIV.
What is Maraviroc?
A CCR5 antagonist used in treatment of HIV.
Which medication types are currently Golden practice for treating HIV?
x2 NRTI and x1 integrase inhibitor.
ART can eliminate infection once HIV-1 has integrated into host DNA - true or false.
False.
Which part of the adrenal gland makes cortisol?
Zona fasciculata.
What does the zona reticularis make?
Androgens.
What may a patient presenting with low blood sugar and low thyroxine have as a condition?
low blood sugar = low cortisol = addison’s
low thyroxine = hypothyroidism
Addison’s + hypothyroidism = Schmidt’s syndrome.
Which is the test for Addison’s?
Short SynACTHen test. = give patient ACTH and cortisol. Adminster 250mcg of ACTH Check cortisol at 30 and 60 minutes. In Addison's, cortisol will stay low despite ACTH injection.
Name three possible adrenal masses.
Phaeochromocytoma
Conn’s syndrome (aldosterone secreting tumour)
Cushing’s syndrome = (cortisol secreting mass)
How do we treat phaeochromocytomas?
Alpha blocker
THEN
beta blocker:
Which is the alpha blocker we use in phaeochromocytoma?
phenoxybenzamine.
In which condition do we use the Dexamethasone suppression test?
Cushing’s syndrome.
What is a normal cortisol level?
<50nM
In a set of results, how can we differentiate between Cushing’s syndrome and Cushing’s disease (pituitary dependent cause)?
Cushing’s syndrome = levels still stay very high
Cushing’s disease = levels decrease but still above range.
Which is the number one cause for Cushing’s syndrome?
Being on oral steroids for something else i.e. another condition.
9am cortisol (Wednesday): 500 nM Given high dose dex suppression 9am cortisol (Friday) 170nM What is the diagnosis?
Cushing’s disease (pituitary dependent).
Name two neoplastic lung diseases
Lung cancer
Mesothelioma (asbestos = main culprit).
Which are the two ways in which we can divide non neoplastic lung disease?
Airway (Asthma, COPD, bronchitis)
Parenchymal (Fibrosing interstitial disease, infection, pulmonary oedema, emphysema).
Define Chronic bronchitis.
Productive cough for most days for at least 3 months over 2 consecutive years.
Define bronchiectasis
Permanent abnormal dilatation of bronchi
Bronchiectasis is not reversible.
Which patients are most at risk of bronchiectasis?
Post infection e.g. cystic fibrosis.
Obstruction in lobe.
What is the main aspect of cystic fibrosis contributing to respiratory disease?
Mucus production.
Name a main cause of pulmonary oedema from the cardiovascular system.
Left ventricular failure.
What is hyaline membrane disease of the newborn?
Lack of surfactant production in neonates = stiff lung.
‘White out’ of lungs on x ray is most commonly due to what?
Alveolar damage (= white infiltrates). 'DAD - diffuse alveolar damage.
Which are the two types of bacterial pneumonia we often refer to? (clue is location).
Lobar pneumonia and Bronchopneumonia.
What is a key difference between bronchopneumonia and lobar pneumonia?
Bronchopneumonia is due to low virulence organisms e.g staphylococcus, streptococcus.
Lobar pneumonia is due to high virulence organisms e.g. pneumococci.
Describe the four stages of lobar pneumonia.
CRGR Congestion; hyperaemia. Red hepatisation (RBCs, fibrin) Grey hepatisation (RBCs break down = exudate) Resolution .
Define emphysema
Permanent loss of the alveolar parenchyma to the terminal bronchiole.
Is Emphysema an airway or parenchymal disease?
Parenchymal disease.
Which protein predisposes one to emphysema?
Deficiency in alpha 1 anti-trypsin.
What is the relationship between smoking and emphysema?
Smoking reduces alpha 1 antitrypsin = an antiprotease = tissue damage (tissues need proteases).
Give 3 causes of granulomatous disease.
Sarcoidosis
IVDU
Infection
What are we talking about when we refer to ‘farmer’s lung’?
Extrinsic allergic alveolitis.
Name the three non-small cell carcinomas
Squamous cell carcinoma
Adenocarcinoma
Large cell carcinoma
What type of cancer is an adenocarcinoma?
Non small cell carcinoma
Are all non small cell carcinomas malignant?
Yes
Which comes first - metaplasia or dysplasia?
Hyperplasia to metaplasia to dysplasia.
What is the main precursor to a adenocarcinoma?
AAH - atypical adenomatous hyperplasia (a lesion).
Are adenocarcinomas mainly central or peripheral compared to squamous cell carcinoma?
Peripheral
Which type of cancer can be targeted more easily with specific drug therapies?
Adenocarcinoma (in contrast, squamous cell carcinomas can get worse with some drug therapies e.g. can haemorrhage).
Generally, which cancer types are more chemosensitive (sensitive to chemotherapy)?
Small cell cancers respond better to chemotherapy than non small cell cancers.
Cetuximab is a cancer therapy targeting which pathway?
EGFR pathway.
An EGFR mutation is most likely to cause which cancer?
Adenocarcinoma
PDL1 expression is commonly seen in which cancer?
Squamous cell carcinoma
What are anal genital warts?
Benign epithelial tumours
Which virus causes anogenital warts?
HPV.
In which part of the skin does most cell replication occur?
Stratum spinosum
HPV codes for how many proteins?
6-8 proteins
Which is the main type of HPV to cause genital warts?
Type 6.
What is the maximum incubation time for HPV?
2 years.
Which is the initial test for female patients presenting with warts?
Speculum examination
Name some causes of a low lymphocyte count
HIV infection
Renal failure
Steroid therapy
Why would you perform an MRI before a lumbar puncture?
Need to exclude a mass lesion if for example the patient is drowsy so do not do LP first = to avoid coning.
Which test is certainly NOT recommended in suspected brain mass lesions?
Lumbar puncture;coning
Which test is certainly NOT recommended in suspected brain mass lesions?
Lumbar puncture; coning
What is coning?
Risk of compression of the lower brain stem as cerebellar tonsils move down through the foramen magnum
Which is the main CNS culprit microorganism for AIDS?
Toxoplasma gondii
What are amphotericin/ fluconazole used to treat?
Fungal infections e.g. cryptococcus.
Give 3 common causes of fever in the traveller -
x1 bacterial
x1 viral
x1 parasitic
Bacterial = Typhoid Viral = Arbovirus (dengue) Parasitic = Malaria
Which virus causes Dengue fever?
Arbovirus
Name two common acute viruses that can present with fever.
Dengue fever HIV seroconversion (when antibodies become detectable)
Give 2 causes of Jaundice in a traveller with fever
Malaria
Leptosporosis
Cholangitis
25 year old female returning from Uganda.
History of fever, mouth sores and rash.
Lymphadenopathy
Fever with rash: think viruses
?EBV
?HIV Seroconversion
What is herpes zoster?
Shingles - cannot become infected if not for having previously had Chickenpox.
What is the main difference between viral meningitis and viral encephalitis?
In viral meningitis, there will be a complete absence of brain function.
What is the normal level for CSF protein?
- 15-0.45g/L
i. e. 150-450mg/L.
> 450mg/L = high protein i.e. viral
Which is the most common cause of viral meningitis vs. viral encephalitis?
Viral meningitis = enteroviruses
Viral encephalitis = Herpes simplex viruses
What is the name of the equation to determine creatinine clearance and which 3 factors are required to calculate these?
Cockcroft-Gault equation
Age
Weight
Serum creatinine
Is bacterial or viral meningitis more common?
Bacterial meningitis.
Is a petechial or purpuric rash common in meningitis?
No; but when it is seen, it is common for meningococcal septicaemia.
When is an EDTA PCR sample performed?
For pneumococcal and meningococcal infection.
What is the first line management for bacterial meningitis?
Broad spectrum antibiotics and steroids.
Which is the most common cause microorganism wise in young adults in bacterial meningitis?
Neisseria Meningitidis.
What caution must we take with sickle cell disease patients?
They are hyposplenic so therefore they are at risk of pneumococcus, meningococcus and haemophilus influenzae B.
When a rash DOES present in Meningitis, what is the likely microorganism?
Meningococcus
Itchy skin, jaundice, aches, fatigue and returned from Egypt having had local food. Not sexually active for past 3 months. What is the diagnosis?
Hepatitis A.
Which is the most common route of transmission for hepatitis A?
Faeco-oral route.
Which is the main test we use to test for hepatitis A?
Serology IgG/ IgM. (but this does not distinguish between new and chronic illness).
How long must a patient be on HIV treatment for before returning to unprotected sex?
6 months
Which is the most common cause of tonsillitis?
Group A Streptococcus.
Which condition is known as the ‘kissing disease’?
infective mononucleosis/ glandular fever (same name both caused by EBV).
Which is the specific test for HIV?
4th generation antibody antigen HIV test
Name three tests we request in querying an STI.
HIV 4th generation test
Hepatitis screen
Syphilis serology
How do we confirm a diagnosis of hepatitis B?
We require a surface antigen rather than just surface and core antibodies; can have Hepatitis B antibody just from begin vaccinated.
What will be positive in a hepatitis B vaccination?
Surface antibody (not antigen). - antigen is if someone actually has hepatitis B.
Lymphocytes in the CSF should make one consider which two conditions?
Encephalitis
Meningitis
Lymphadenopathy, fever, splenomegaly and lymphocytosis should make one consider which diagnosis?
Glandular fever is the same thing as infective mononucleosis (caused by EBV).
Fever, symmetrical facial swelling, headache, neck stiffness. What is the likely diagnosis?
Mumps virus; symmetrical facial swelling. Mumps is a notifiable disease BTW.
In Hepatitis serology, how would we gauge that the patient currently has active disease?
A positive HBV sAg (surface antigen) - confirmed by body antigen.
Which is the most likely route of transmission for Hepatitis B?
Sexual contact
Give 3 facts about Hepatitis B including incubation period.
8 genotypes DNA virus Sexual contact Incubation period - 1-6 months. Treat with nucleoside analogue: Tenofovir
From hepatitis serology, how can we tell if a patient is non infectious?
Surface antigen negative: HBV sAg -ve
What do we use to treat Hepatitis B?
Tenofovir.
When is HBV (hepatitis B) infection classed as chronic?
When longer than 6 months.
Hepatitis B Infected mothers can continue to breast feed as there is no additional risk of transmission. True or false.
True.
(Vertical transmission is 90% common from mother to baby when mother is eAg positive). - 10% common when mother is surface antigen positive.
With which hepatitis can you get hepatitis D?
Hepatitis B.
Give 3 typical ways a patient with Malaria can present.
Cerebral involvement (dizzy, drowsy)
Anaemia
Renal failure
Hypoglycaemia
Which is the preferred treatment for malaria?
IV artesunate
What is the most common cause of a purpuric rash? - Purpura Fulminans?
Meningococcal sepsis
secondly pneumococcal sepsis and staphylococcus sepsis
What is the first line of treatment for Meningococcal sepsis?
Ceftriaxone for N. Meningitidis
- if N. Meningitidis is the KNOWN cause, treat with benzylpenicillin.
Which class of drugs is Ceftriaxone?
Cephalosporin
Why would we not use clarithromycin in cholecystitis?
Does not cover gut bacteria.
Which bacteria would we use to cover most gram negative bacteria and anaerobes?
Co-amoxiclav
Gentamicin is in which class of antibiotics?
Aminoglycoside
Which causes a rash - Mumps or measles?
Measles. Mumps does not cause a rash.
Name three conditions which could present with a maculopapular rash.
Measles
HIV
Rubella
Hand foot and mouth disease.
Give 3 causes of granulomatous inflammation in the liver.
Sarcoidosis
Tuberculosis
Schistomiasis
Drug-induced
What type of amyloid is associated with multiple myeloma?
AL - light chain amyloid.
Give 3 different causes of liver damage due to alcohol.
Steatosis
Steatohepatitis (more ballooning and fibrosis associated compared with steatosis).
Cirrhosis
Give an example of a monogenic autoinflammatory disease.
Familial Mediterranean fever
Give an example of a monogenic autoimmune disease.
FOX P3 IPEX (immune regulation, polyendocrinopathy, enteropathy, X-linked syndrome).
Which type of condition is Crohn’s disease?
Polygenic inflammatory.
In which conditions (generally) are HLA associated?
Autoimmune
What is Hashimoto’s disease?
The most common form of hypothyroidism.
Which is the best marker for rheumatoid arthritis?
Anti CCP (rather than rheumatoid factor).
What is MC&S?
Microscopy, culture and sensitivity.
What is the difference between colonisation and infection?
Colonisation = bacteria multiply with no host response Infection = bacteria multiply WITH host response.
What is the difference between culture and sensitivity?
Culture = identification of a bacteria Sensitivity = identifying which antibiotics are most suitable.
In gram stain, what are purple cells?
Gram positive.
Name a yeast which causes Meningitis.
Cryptococcus meningitis. (cryptococcal neoformans = encapsulated yeast i.e.fungus).
Which microorganism causes slapped cheek syndrome?
Parvovirus B19. - erythema infectiosum.
How would you differentiate between Malaria and Hepatitis A presentation. Also consider what are their typical presentations.
Typically both = fever, malaise, jaundice. splenomegaly.
Malaria = shorter, maybe 3 days.
Hepatitis A = longer incubation period, few weeks.
Hepatitis A = severe jaundice.
What is the normal range for CD4+ cell count?
500 - 1500 cell/mm^3
A patient with a CD4+ count of <200cell/mm^3 will require what for their treatment?
HAART and co-trimoxazole to cover against pneumocystis jiroveci pneumonia.
Name the medication we use to treat Pneumocystis Jiroveci?
Co-Trimoxazole.
Name the medication used to treat Meningococcal meningitis prophylactically.
Ciprofloxacin.
Which medication should not be taken during breastfeeding?
Codeine.
Name the emergency contraception medication.
Levonorgestrel
Which is the medication of choice if a patient is allergic to penicillin?
Doxycycline, clarithromycin.
What type of bacteria is Neisseria Gonorrhoea?
Gram negative coccus
What are the signs of Gonorrhoea in men?
Urethral discharge and dysuria.
Which drug class does Ciprofloxacin belong to?
Fluoroquinolone
With regards to Glandular fever, what is the main advice we would give patients playing sports?
Do not play contact sports for 4 weeks.
Name the largest risk factor for colonic carcinoma
Ulcerative Colitis
Describe Ulcerative Colitis’ inflammation.
Inflammation confined to the mucosa.
Describe Crohn’s inflammation.
Transmural inflammation
In a patient with diarrhoea with C. difficile as the likely cause, how do we treat?
Oral vancomycin
What is the relationship between cortisol and potassium?
Cortisol causes hypokalaemia
High cortisol = low potassium
Does alkalosis cause hyper or hypokalaemia?
Hypokalaemia
How would we differentiate between ATN and glomerula disease?
Renal biopsy.
Name the 3 causes of Cushing’s disease
Pituitary
Ectopic ACTH
Adrenal tumour
Which cause of Cushing’s disease is associated with hypokalaemia?
Ectopic ACTH; Cortisol is very high
High Cortisol = low potassium
What is the most frequent brain tumour in adults?
Metastatic deposit
What is the most frequent brain tumour in children?
Pilocytic astrocytoma
What does the tumour grade tell us?:
Therapy response
Disease Spread
Survival
Cell of origin
Survival
Which mutation identifies astrocytic tumours with a better prognosis?
IDH mutation
5 year old headache, vomiting and papilloedema with cystic lesion. Diagnosis?
Pilocytic astrocytoma (common in children. Meningiomas uncommon in children).
70 year old with left arm and leg weakness and then seizure. MRI shows heterogeneous enhancing right frontal lesion. Diagnosis?
Glioblastoma grade 4.
What will ‘compensated’ mean in arterial blood gases
The pH is normally improved whereas the PC02 then has to increase
Which are the two types of oedema?
Vasogenic (damages BBB) and Cytotoxic (cellular injury)
Which are the two types of hydrocephalus?
Non-communicating = obstruction of CSF flow Communicating = no obstruction. Problem is with reabsorption of CSF into venous sinuses.
What are the consequences of raised ICP on the brain?
Forces brain against the skull and inflexible dural folds = results in herniation of brain where there is space available.
Which are the two kinds of stroke?
haemorrhagic and infarct
Is subdural haemorrhage classified as a stroke?
No. Only subarachnoid haemorrhage (SAH)
What is the average duration of a TIA?
1 minute. Most TIAs last less than five minutes.
There is permanent damage to the brain when a TIA is over. True or false?
False; this is the case with stroke, not TIA.
Most strokes are due to infarct or haemorrhage?
Infarct
What is a contusion?
Brain in collision with the skull
What is the commonest cause of a coma?
Diffuse axonal injury
In which condition do we see heinz bodies?
Glucose-6-phosphate dehydrogenase deficiency
In which conditions do we see Howell-Jolly bodies? What do they look like?
Sickle cell disease
Hyposplenism
Megaloblastic anaemia
Basophilic (purple spot) nuclear remnants in RBCs.
What are reticulocytes?
Immature RBCs.
What does right shift mean?
Hypermature white cells
What is rouleaux formation? Where may we see it?
Stacked RBCs - myeloma
What is the name of the fragmented parts of RBCs - irregularly shaped with sharp edges? In which condition are these soon?
Schistocytes seen in DIC, HUS (haemolytic uraemic syndrome), TTP.
What is the name of the cell bull’s eye appearance with central pallor? Where may these be seen?
Target cell - seen in Liver disease, hyposplenism.
What is often the cause of high MCV?
Decreased production of RBCs. This is why folate/B12 deficiency result in macrocytic anaemias - B12 and folate are required for RBC production.
Give two conditions which result in low MCV.
Iron deficiency, thalassaemia.
ACD - Anaemia of chronic disease
Which condition would show normal MCV?
Acute blood loss.
Give 3 ways Iron deficiency anaemia may present on the blood film.
Poikilocytosis
Anisocytosis
Microcytosis
Hypochromic cells
Which are the first investigations to assess iron deficiency anaemia
OGD, colonoscopy, urine dip, coeliac investigation.
What is ACD? What is Anaemia of Chronic disease?
Inhibition of RBCs driven by cytokines e.g. TNF-alpha (reduces EPO synthesis).
Give 2 causes of anaemia of chronic disease.
Chronic infection e.g. TB
Rheumatoid arthritis
Malignancy.
Is ferritin high or low in ACD?
High.
What is the difference between iron deficiency and anaemia of chronic disease in terms of iron and ferritin?
Iron deficiency; Low iron, low ferritin, high TIBC.
Anaemia of chronic disease; Low iron, high ferritin, low TIBC.
What are iron levels usually like in pregnancy?
High.
Which cell is characteristically low in aplastic anaemia?
Reticulocyte count
How will MCV look in Alcohol?
High MCV.
Which is the most common cause of macrocytosis without anaemia?
Alcohol
What does a megaloblastic blood film look like?
Hypersegmented polymorphs, leucopenia, macrocytosis.
What is the name of the condition in which there is B12 deficiency? What can we give to treat?
Pernicious anaemia. Give vitamin B12 in form of hydroxocobalamin.
Which is the test we use to diagnose Pernicious anaemia.
Parietal cell antibodies.
How do haemolytic anaemias present in terms of markers?
Raised unconjugated bilirubin, LDH, Hb (; increased breakdown of RBCs).
Which marker is raised in haemolytic anaemia?
Raised unconjugated bilirubin
Parvovirus B19 can cause what?
Aplastic crisis
Sickle cell disease and thalassaemia are examples of which type of condition?
Haemoglobinopathies
Hereditary spherocytosis is what kind of defect?
Membrane defect
What is the main cause of hereditary spherocytosis?
Spectrin/ ankyrin deficiency.
How can we treat spherocytosis?
Splenectomy, folic acid.
Name three causes of haemolytic anaemias
Membrane defects e.g. Hereditary spherocytosis, elliptocytosis
Enzyme defects e.g. G6PD deficiency, pyruvate deficiency
Haemoglobinopathies e.g. sickle cell disease, beta thalassaemia
Non inherited causes include drugs, alloimmune e.g. haemolytic transfusion reactions.
How do we treat hereditary spherocytosis?
Splenectomy and Folic acid.
Which is the commonest RBC enzyme defect?
Glucose-6-phosphate dehydrogenase deficiency.
What is Glucose-6-phosphate dehydrogenase deficiency? G6PD. Which cell is associated with it?
X linked RBC enzyme defect.
Rapid anaemia and jaundice
Heinz bodies
Dark urine; intravascular haemolysis
What is the cause of dark urine in Glucose-6-phosphate dehydrogenase deficiency?
Intravascular haemolysis
Which foods can precipitate Glucose-6-phosphate dehydrogenase deficiency?
Fava broad beans; an oxidant
What are the clinical features of pyruvate kinase deficiency?
Neonatal Jaundice
Splenomegaly
Haemolytic anaemia
Describe the difference in structure between HbA, HbA2 and HbF.
HbA - 2 alpha, 2 beta
HbA2 = 2 alpha, 2 gamma
HbF = 2 alpha, 2 delta
Which globin chain is affected in sickle cell disease and beta thalassaemia?
Beta globin chain.
Are haemoglobinopathies autosomal dominant or recessive?
Autosomal recessive.
What is the cause of sickle cell disease?
GAG-GTG mutation.
Glu - Val mutation at 6th amino acid on beta chain.
HbS instead of HbA.
What is HbAS compared with HbSS?
HbAS = sickle cell trait HbSS = Sickle cell anaemia
When does sickle cell disease manifest?
3-6 months; reduction in foetal HbF.
Name three features of sickle cell disease.
Anaemia
Splenomegaly
Folate deficiency
How do we diagnose sickle cell anaemia?
Blood film
Hb electrophoresis
Guthrie test (at birth)
How do we treat sickle cell anaemia?
Analgesia
Blood transfusion in severe crises
All chronic patients should be on penicillin.
Folic acid and hydroxycarbamide (which will increase HbF).
How do we diagnose Beta thalassaemia?
Hb electrophoresis and Guthrie test.
What is the presentation of beta thalassaemia?
Skull bossing, maxillary hyptertrophy, hepatosplenomegaly.
How do we treat beta thalassaemia?
Blood transfusions with iron chelation.
Folic acid.
What is the difference between alpha and beta thalassaemia?
Alpha thalassaemia = excess beta chains
Beta thalassaemia = excess alpha chains.
What is the Coombs test?
Coombs/ antiglobulin test (AGT)/ DAT (direct antiglobulin test).
Coombs test checks for antibodies against RBCs.
DAT = identifies haemolytic anaemia. Positive = agglutination. Indirect = only in prenatal testing (more prevention).
What is MAHA? Which is the key cell?
Microangiopathic haemolytic anaemia = Mechanical RBC destruction.
Key cell = schistocytes.
What is HUS? Which organism causes it? Give a patient’s presentation.
Haemolytic uraemic syndrome. Caused by E.Coli
E.Coli toxin damages endothelial cells and RBCs.
MAHA, DIARRHOEA, RENAL FAILURE.
Which factor do we need to trigger the coagulation cascade?
Tissue factor.
Which factors convert prothrombin to thrombin?
Va (5a), Calcium and platelet factor.
Which factor converts Fibrinogen to fibrin?
Thrombin.
APTT Vs. PT Vs TT measure which part of the coagulation cascade? What do these stand for?
APTT (activated partial thromboplastin time) = intrinsic pathway
PT (prothrombin time) = extrinsic pathway
TT (thrombin time) = common pathway
Which factor does the intrinsic pathway start off with compared with the extrinsic pathway?
Intrinsic pathway starts with factor 12
Extrinsic pathway starts with factor 7
APTT measures which part of the coagulation cascade?
The intrinsic pathway.
Name three causes of thrombocytopenia.
Bone marrow failure
AITP - autoimmune thrombocytopenia purpura
Drugs e.g. heparin.
What is the cause of Haemophilia A?
Factor 8 (VIII) deficiency X linked (affects mainly males)
Why is the APTT prolonged but the PT is normal in Haemophilia A?
Haemophilia A = F8 deficiency. F8 is in the intrinsic pathway. APTT relates to intrinsic pathway only.
Which pathway does PT measure?
The extrinsic pathway.
What will blood tests look like in Haemophilia A?
Prolonged APTT
Normal PT
Low Factor VIII assay.
What is Haemophilia B?
Factor 9 deficiency.
What will APTT and PT look like in Haemophilia B?
Prolonged APTT ; Factor 9 is in the intrinsic pathway.
Normal PT.
Which are the main factors in the extrinsic factor?
Factors 5 and 7. (Haemophilia is affected by factors 8/9 in the intrinsic pathway).
Which factor is affected in Von Willebrand’s disease?
Factor 8 (VIII). Reduced F8 as F8 carries vwf.
Which is prolonged in vWF - APTT or PT?
Prolonged APTT; Factor 8 (in the intrinsic pathway) carries vWF.
What is DIC?
Widespread coagulation. Can be caused by malignancy, sepsis, trauma.
Hyperclotting.
Vitamin K is needed for the synthesis of which factors?
2, 7,9,10.
Give 2 causes of Vitamin K deficiency
- Warfarin
2. Malabsorption, malnutrition of Vitamin K.
Despite using mainly APTT for much of the clotting disorders, when would we need PT?
Disseminated intravascular coagulation.
Which are the three factors of Virchow’s triad?
Hyper coagulability
Endothelial stability (vessel wall)
Stasis (flow)
What is the Wells score used to measure?
Pulmonary embolism and DVT..
After a high Well’s score, which tests should be performed? What does the Well’s score assess?
Assessing an individual’s risk for DVT, PE.
High Well’s: Ultrasound for DVT risk in limb. CTPA for PE.
Which treatment is involved in DVT prophylaxis?
Low molecular weight heparin, TED stockings.
How does heparin work?
Inactivating thrombin. Side effect = bleeding, thrombocytopenia.
What is the target INR?
- 5 for first episode of DVT
3. 5 for recurrent DVT/ PE.
Name four haematological changes in pregnancy.
Reduced Hb, platelets, Protein S.
Increased red cell mass, plasma volume.
How does haemolytic disease of the newborn occur?
antibodies from mother - often Anti-D cross the placenta and correspond to foetus’ red cells which have the antigen = destroys the red blood cells. Causes anaemia and jaundice.
Always transfuse RhD negative blood.
Which pathway will affected in Haemophilia A and which will be normal?
apTT; F8/F9 deficiency in the intrinsic pathway Normal PT (extrinsic pathway)
Spherocytosis and a positive Coomb’s test is indicative of what?
Haemolytic anaemia.
How can AML be classified?
Myeloid or lymphoid.
Acute or chronic.
Name 3 ways in which acute leukaemia is characterised?
Immature blast cells
Bone marrow failure
Name three ways in which bone marrow failure can present in a patient.
Anaemia = pallor Thrombocytopenia = bleeding Neutropenia = infection
On a blood film, what do we typically see in AML?
Auer Rods, granules; myeloid and blast cells.
Which two investigations do we use to investigate AML?
Cytogenetics and FISH.
What is involved in a coagulation screen?
PT and thrombin time (does not include platelets)
Auer rods can be definitive of myeloid. True or false?
True.
Name two clinical features of AML.
Splenomegaly
Hepatomegaly.
Which cell typically shows granules - lymphoblastic or myeloid?
Myeloid.
Name two causes of high MCV.
B12, folate deficiency.
Which marker will be definitively low in DIC?
Fibrinogen.
How do we treat polycythaemia vera?
Venesection and hydroxycarbamide
What is Polycythaemia vera caused by?
JAK2 mutation.
What does bone marrow aspirate look at?
Blast cells
Erythroblasts
What is the main issue in AML in terms of mechanism?
Dysfunction in transcription factors during leukaemogenesis - but requires 2 hits.
Which test would you do to differentiate between AML and ALL?
Immunophenotyping
Give x3 features of AML
Bone marrow failure i.e. bleeding, anaemia, infection.
DIC
When would you require a bone marrow aspirate?
When there is aleukaemic picture
How do we treat AML?
Red cells, platelets, fresh frozen plasma, allopurinol, chemotherapy.
Why does cytogenetic/molecular genetic category matter in treating AML vs ALL?
Ph-positive need imatinib
What is Imatinib?
A tyrosine kinase inhibitor
Name two consequences of Salpingitis.
Infertility
Ectopic pregnancy
What is a polyp?
Benign hyperplastic growth - can lead to bleeding, discharge.
Name the risk factors for cervical cancer
HPV
Many sexual partners
smoking
What is CIN?
Cervical intraepithelial neoplasia
Dysplasia in the Squamous epithelium
Which is the most common cervical carcinoma type?
Squamous > adenocarcinoma
What is latent HPV infection?
HPV stays in the basal cells where infection is not produced. HPV effects are not seen.
How does HPV transform the normal cell?
2 proteins are encoded by the virus - E6 and E7.
They bind to tumour suppressor genes (P53 and Rb) and inactivate them = inhibits apoptosis.
How does HPV appear in patients?
Often body eliminates infection within 2 years.
Few symptoms, body eliminates HPV by itself.
However when persistent - can cause cancer.
How often does cervical screening occur?
25-49 - 3 yearly
50+ = 5 yearly.
sample from cervix.
What is the HPV DNA test?
Uses RNA probes to look between low risk and high risk HPV.
When is the HPV vaccine offered?
1st dose in year 8
2nd dose 6-24 months after first.
Give 2 indications for a uterine biopsy.
Infertility
Uterine bleeding.
Which is the most common gynaecological cancer in women?
Gynaecological cancer
Give two risk factors for gynaecological cancer
Nulliparity
Obesity
What is a leiomyoma?
Tumour of the smooth muscle.
Which is the medical term for fibroid?
Mesenchymal tumours leiomyoma
How do we define the malignant tumours of the smooth muscle?
Leiomyosarcoma
What actually is endometriosis?
Endometrial glands and stroma outside of the uterus
How do we classify ovarian tumours?
Primary -epithelial (different types e.g. serous, mucinous). -germ cell -sex cord Secondary
Which are the commonest ovarian tumour?
Epithelial tumours.
Name two risk factors for ovarian cancers.
Nulliparity and infertility
What is Lynch syndrome?
HNPCC syndrome
BRCA mutations are usually associated with low or high grade tumours?
High grade tumours. Low grade are more associated with KRAS, BRAF.
When will a tumour be classified as mucinous?
Displays morphology similar to cells of the GI tract.
Which part of the female genital tract is the commonest to receive metastatic tumours?
Ovaries
Pelger-Huet cells and ringed sideroblasts on blood film are characteristic of which condition?
Myelodysplastic syndrome
Auer rods are characteristic of what?
Acute myeloid leukaemia
Give some characteristics of MDS (myelodysplastic syndrome).
Number of cytopenias (Hb, neutrophils, monocytes, platelets all «<
What is the main cause of MDS?
Mutations in TP53 and other tumour suppressor genes.
How do we treat MDS?
- Product support to replace platelets, Hb. - Blood product support.
Antimicrobial therapy.
Growth factors
Stem cell transplantation
Chemotherapy
(not widely treated with either however).
Which oral chemotherapy may we use in the treatment of MDS?
Hydroxyurea
The primary treatment of MDS is intensive chemotherapy. True or false?
False.
What is aplastic anaemia?
Stem cell problem where the bone marrow cannot produce blood cells.
Name the triad of aplastic anaemia.
Anaemia (pallor), leucopenia (infections) and platelets (bleeding)
Give 3 differentials of pancytopenia
Aplastic anaemia
AML
Idiopathic thrombocytopenic purpura
How do we diagnose aplastic anaemia?
Camitta criteria
Reticulocytes, neutrophils, platelets «
Name one key pancytopenia.
Fanconi anaemia
What is fanconi anaemia?
The most common form of inherited aplastic anaemia.
Which is the most common aspect of dyskarytosis congenita?
Telomere shortening
What is the incubation period for
- bacteria
- viruses
- parasites?
Define Gastroenteritis.
Rapid onset, diarrhoea less than 2 weeks.
Loose stool >3 times a day.
How will a patient present differently if their diarrhoea is caused by Vibrio cholerae vs. salmonella/campylobacter jejuni?
Vibrio cholerae = no fever
Salmonella = fever
In a patient who has had watery diarrhoea with fever for 1-6 hours, which bacterium is the likely culprit?
Staphylococcus aureus.
Which pathogenic virus has the longest incubation period?
Norovirus; 24-48 hours.
Which pathogen is associated with molluscs and shellfish?
Norovirus
Which pathogen is associated with meats, hot dogs and soft cheese?
Listeria monocytogenes.
Which pathogen is associated with faecally contaminated food or water?
E.Coli.
Which pathogen is associated with poultry, eggs, and unpasteurised milk?
Salmonella
How does the mechanism of cholera work?
Adenylate cyclase becomes activated which opens Cl- channel at the apical membrane of enterocytes. Efflux of Cl into the lumen = loss of H20 and electrolytes.
How do superantigens work?
They bind directly to T-cell receptors and MHC molecules. This produces a massive cytokine response IL-1 and IL-2, CD4+ cells.
What is the difference between inflammatory diarrhoea and enteric fever?
Inflammatory diarrhoea (exudate) = septic shock, neutrophilia Enteric fever = no septic shock, no neutrophilia
Which bacteria causes enteric fever?
S. Typhi
In a patient vomiting with diarrhoea lasting 2-3 days, which is the most suspected pathogen?
Norovirus.
Haemolytic anaemia is an extra-intestinal manifestation of which pathogen?
Campylobacter Jejuni.
Meningitis is an extra-intestinal manifestation of which pathogens?
Listeria, salmonella.
Reheated fried rice, which is the pathogen responsible?
Bacillus cereus. (gram positive rods).
Food is not cooked to a high enough temperature - which is the microorganism responsible? What can the bacteria cause as a complication?
Bacillus cereus - not destroyed by reheating. Cerebral abscesses as a complication.
Which bacteria causes food poisoning from reheating food - but specifically reheating meat?
Clostridium pefringens.
Which microorganism is actually inactivated by cooking?
Clostridium botulinum.
Pseudomembranous colitis is caused by which pathogen? Which toxins does this pathogen cause?
Clostridium difficile. Toxin A (enterotoxin) Toxin B (cytotoxin)
How do we best manage colitis?
Vancomycin - stop antibiotics.
Which pathogen typically grows on refrigerated food? How do we treat?
Listeria monocytogenes.
Treat with Amoxicillin
Which bacteria is responsible for Traveller’s diarrhoea?
E. Coli.
Which is the main type of E. Coli to cause traveller’s diarrhoea?
Enterotoxigenic E. Coli (ETEC).
Which antibiotic is used for the vibrio pathogens?
Doxycycline
How does Campylobacter present?
Watery, foul smelling diarrhoea, bloody stool, fever, abdominal pain.
Giardia lamblia is what type of microorganism? How do we treat it?
Protozoa. Treat with Metronidazole.
The rotavirus presents for approximately how long? Who does the virus typically effect?
3-8 days. Typically affecting children aged 6 months - 2 years.
Which condition between osteomalacia, paget’s disease, sarcoidosis and osteoporosis causes hypercalcaemia?
Sarcoidosis.
Which antibiotic is used to treat pseudomonas auerginosa?
Gentamicin (an aminoglycoside) and Ciprofloxacin (broad spectrum antibiotic).
Which inflammatory disease affects the large bowel and duodenum?
Crohn’s disease
The Breslow score is used to measure which condition?
Melanoma
Where is the enzyme 25-hydroxylase found?
Liver
Which is the antibiotic of choice in Diabetes with cellulitis?
Flucloxacillin - to cover staphylococcus and streptococcus.
Which is the best marker of liver damage following paracetamol overdose?
Prothrombin time
During pregnancy, what happens to the platelet count?
Platelet = reduces
What are the normal changes to full blood count in pregnancy?
Mild anaemia, macrocytosis (increase in red cell mass) and neutrophilia
what is the normal range for platelet count?
Between 150-400x10^9/L
Give 3 causes of thrombocytopenia in pregnancy.
Pre-eclampsia
ITP - Immune thrombocytopenic purpura
DIC
How do we treat ITP
IV immunoglobulin
Steroids
for bleeding
What is MAHA?
Red cell destruction due to platelets building up in blood vessels.
microangiopathic haemolytic anaemia.
What are the coagulation changes during pregnancy?
Rise in vWF and factor VII, VIII = increased rate of thrombosis.
Fall in protein S.
Which tests would we request to look at thromboembolic disease in pregnancy?
Doppler and VQ scan
How do we define post-partum haemorrhage?
> 500mL blood loss
What is the main purpose of haemoglobinopathy screening?
To avoid birth of children with a0 thalassaemia *not compatible with life).
To avoid sickle cell disease
What is the difference between iron deficiency and thalassaemia trait?
RBCs are raised in thalassaemia trait whereas low or normal in iron deficiency anaemia.
In gestational thrombocytopenia, the baby’s platelets can be affected. True or false?
False.
When do you restart LWMH after delivery?
Name one common cause of post partum haemorrhage.
Uterine atony
What are myeloblasts?
Precursors of myeloid cells (immature myeloid cells) - often seen in acute infection.
What is a normal percentage of myeloblasts?
What is the next stage of abnormal myeloid cells?
What about when there are too many myeloblasts?
Normal percentage = <5%
5-20% = Myelodysplasia
>20% = AML
What is the name of the stage in between a normal percentage of myeloblasts up to AML?
Myelodysplasia
What is the percentage of lymphoblasts in ALL
> 20%
Which are the B cell markers?
CD19+, CD20+
Which cell is in excess in the bone marrow in myeloma?
Plasma cells
Are Bence Jones Proteins usually seen in urine?
No; in multiple myeloma we we will see them as free chains in the urine.
How will ITP (Immune thrombocytopenia purpura present on blood tests?
Low platelets = easy bleeding, easy bruising.
How will ALL present on blood tests?
Low neutrophils, low white cell count, high MCV.
How may ITP differ from ALL in the patient’s blood test markers?
ALL = low white cell count and low neutrophils whereas ITP shows normal white cell count.
Where reticulocytes are raised, what should the key diagnosis in your head be?
Haemolytic anaemia - inherited or acquired.
Which haemolytic anaemia is caused by a defect in the RBC membrane?
Hereditary Spherocytosis.
Which haemolytic anaemia is caused by a defect in the RBC enzyme?
Glucose-6-phosphate deficiency (G6PD).
How do we diagnose Hereditary spherocytosis?
DAT -ve (the guthrie test) and blood film to check for spherocytes.
How do we diagnose Sickle cell anaemia?
Electrophoresis.
How may one acquire a haemolytic anaemia?
Auto or allo
Auto - being linked to immune disease
Allo - linked to blood transfusion
When would a DAT test be positive vs. negative?
DAT positive (DAT +ve) = acquired haemolytic anaemia DAT negative (DAT -ve) = inherited haemolytic anaemia e.g. hereditary spherocytosis
How do we differentiate between iron deficiency and anaemia of chronic disease (ACD)?
Iron deficiency = Normal/ low ferritin. High transferrin
ACD = Normal/ high ferritin. Low transferrin.
Transferrin is the differentiator.
Which is the one marker which is high in iron deficiency?
Transferrin. (This is different to transferrin saturation which will still be low in iron deficiency). Transferrin = HIGH in Fe2+ deficiency.
What is anaemic of chronic disease (ACD)?
Iron stores are normal but sequestered and unavailable for erythropoeisis.
Hence, high hepcidin; hepcidin sequesters iron.
Which are the haematinics?
Iron, B12, folate.
Patient presents with pancytopaenia. Give 3 differentials.
Bone marrow failure
Non malignant: DNA synthesis failure, aplastic anaemia
Malignant: cancers spreading to the bone marrow
*non haematological = breast/ prostate
*haematological = leukaemia, myeloma, lymphoma.
Give two causes of pancytopaenia
Aplastic anaemia
Haematological cancers: leukaemia, myeloma, lymphoma
How can CML present in patients? And on examination?
Lethargy and bleeding. On examination, hepatosplenomegaly.
What are blood cell markers like in CML?
Leukocytes
Neutrophils
Myelocytes (myeloblasts if not chronic)
Which translocation produces the Philadelphia chromosome? And which gene is produced as a result? How does this relate to cancer?
9:22 = produces the ABL-BCR fusion gene. Encodes the 210 kDA protein which increases TK (tyrosine kinase) activity = cancerous.
Which is the best prognostic factor as a marker to look for in CLL?
The TP53 mutation.
Name two targeted therapies for CLL?
BCR-ABL Kinase inhibitors (Ibrutinib) BLL2 Inhibitor (Venetoclax)
Venetoclax is what type of cancer class therapy and is used to treat which cancer?
BLL2 inhibitor - used in CLL.
The BCR-ABL fusion gene causes which cancer?
CML - Chronic lymphocytic leukaemia.
What is involved in a myeloma screen?
IgA, IgM, IgG, Calcium.
Give an example of a phosphodiesterase inhibitor
Sildenafil.
Listeria monocytogenes is what kind of bacteria?
Gram positive
Allopurinol is contraindicated with which drug and why?
Allopurinol is contraindicated with azathioprine; allopurinol interferes with the metabolism of azathioprine and increases mercaptopurine levels.
Allopurinol inhibits xanthine oxidase.
Xanthine oxidase is responsible for inactivating mercaptopurine.
= Risks bone marrow suppression.
How does the treatment of acute gout compare with chronic gout?
Acute gout = Colchicine
Chronic gout = Allopurinol
Liver damage following paracetamol overdose is best diagnosed by which marker?
Prothrombin time.
CD20+, EBV+, ‘starry sky’ appearance is indicative of which cancer?
Burkitt’s lymphoma.
What is the difference between sensitivity and specificity?
Sensitivity - Correctly identifying patients with a disease
Specificity - Correctly identifying people without a disease
Starry sky appearance on blood film is diagnostic of what condition?
Burkitt’s lymphoma.
Which infection is most common amongst IV drug users?
Hepatitis C
Which factor is deficient in Haemophilia A and Haemophilia B?
Haemophilia A = Factor VIII deficiency (8)
Haemophilia B = Factor IX deficiency (9)
What is Disseminated intravascular coagulation (DIC)?
Give x2 causes of DIC.
Widespread activation of coagulation but clotting factors and platelets are consumed so there is increased risk of bleeding.
Causes: Malignancy, sepsis, trauma, toxins.
Vitamin K is needed for synthesis of which factors?
Factors 2, 7, 9, 10.
What do we use to treat DVT/ PE?
- LMWH and warfarin
or 2. DOAC e.g. Apixaban
LMWH will be stopped once INR is in the therapeutic range (2-3).
Treatment for 3 months minimum.
What is the mechanism by which heparin works?
Activates antithrombin = inhibits thrombin and factors 9,10,11.
What is haemolytic disease of the newborn?
Where maternal antibody (most typically anti D antibody) is high it can destroy foetal red cells if they have the corresponding antigen.
What are the main clinical features of acute leukaemia?
Bone marrow failure = always comes with:
- Anaemia
- Infection (neutropenia)
- Bleeding (thrombocytopenia)
What exactly is immunophenotyping?
Looking at the different markers cells express. This is really useful in AML vs ALL. myeloid vs lymphocyte.
In flow cytometry, how will ALL vs AML present?
Different markers. ALL = lymphocytes so B and T cell markers (CD19, CD3, CD4, CD8)
AML = myeloid markers - CD33+
How is chronic myeloid leukaemia often diagnosed?
Large number of differentiated neutrophils.
What is the main treatment for CML?
Imatinib - 95% remission rate!!!
On examination what is the main finding of CML?
Splenomegaly - often massive.
The Philadelphia chromosome (9;22) caused by the fusion gene BCR-ABL is often diagnostic for which condition?
CML - Chronic myeloid leukaemia.
Which are the three phases of CML?
Chronic (<5% blasts)
Accelerated (>10% blasts)
Blast (>20%)
Which phase of CML is most receptive to Imatinib as a therapy?
Chronic phase
Smear cells are seen in which diagnosis?
CLL - Chronic lymphocytic leukaemia.
Which marker is a key prognostic factor for Chronic lymphocytic leukaemia? (CLL)
LDH
The chronic, accelerated and blast phases describe which cancer?
Chronic myeloid leukaemia (CML)
What is a lymphoma?
A neoplastic tumour of lymphoid tumour.
Which is more common - Hodgkin’s or non-hodgkin’s lymphoma?
Non-hodgkin’s lymphoma.
How does Hodgkin’s lymphoma present?
Asymmetrical lymphadenopathy B symptoms: - weight loss <10% unintentional in 6 months - Fever - Night sweats
Which lymphoma is EBV related?
Hodgkin’s lymphoma
The Reed Sternberg cell is seen in which cancer?
Hodgkin’s lymphoma - a binucleate cell
What is the name of the staging system which describes stages 1-4 for cancer?
Ann-Arbor system
Patient involvement with 3 Lymph node regions above the diaphragm but no weight loss or night sweats would be which staging on Ann Arbor?
2A (A because no constitutional symptoms otherwise would be B)
What is the treatment for Hodgkin’s lymphoma?
ABVD Adriamycin Bleomycin Vinblastine Dacarbazine
(2-4 cycles in stage 1/2, 6-8 cycles in stage 3/4).
What is the difference between autologous and allogeneic SCT?
Autologous = patient's own stem cells Allogeneic = HLA-matches stem cells
Name the 3 HIGH GRADE types of Non-hodgkin’s lymphoma.
Burkitt’s
Diffuse large B cell
Mantle cell
Low grade = marginal zone
Is Marginal zone high or low grade and which type of lymphoma?
Low grade non-hodgkin’s lymphoma
What is Burkitt’s characterised by on histology?
Starry sky appearance
How do we treat Burkitt’s lymphoma?
Chemotherapy - rituximab = anti CD20+
Which is the chemotherapy treatment of choice for most non hodgkin’s lymphomas?
Rituximab
Which are the three types of Burkitt’s lymphoma?
Endemic: EBV associated, Africa
Sporadic: EBV associated, outside of africa
Immunodeficiency: Not EBV associated
How do we treat MALT?
Remove antigenic stimulus - often due to H pylori. So H. Pylori triple therapy.
Rituximab is anti which marker?
CD20+
Which medication is used against T cell lymphomas?
Alemtuzumab (anti CD 52).
Define multiple myeloma. Production of antibodies - IgG being the most common
Neoplasm of plasma cells
What are the clinical features of multiple myeloma?
CRAB Calcium Renal failure Anaemia Bone pain, osteoporosis, osteolytic lesions, fractures.
How does multiple myeloma typically present on blood film?
Rouleaux formation (RBC stacking)
BJPs in urine
High ESR
main treatment = bisphosphanates for CRAB symptoms.
Where are CRAB symptoms seen and which treatment can we use for them?
Multiple myeloma.
Bisphosphanates.
What is amyloidosis?
Misfold of proteins - kappa: lambda light chain ratio affected.
How do we differentiate between myelodysplastic syndromes and acute myeloid leukaemia?
Blast number.
Myelodysplastic = <20% blasts
Acute leukaemia = >20% blasts
What are ring sideroblasts and where can they be seen?
Ring around the nucleus of the cell
MDS (myelodysplastic syndrome)
Name 3 forms of treatment that could be used for myelodysplastic syndromes.
EPO transfusion, antibiotics
Chemotherapy
Allogenic transplant
What is aplastic anaemia?
Inability of bone marrow to produce blood cells. 70% idiopathic.
Symptoms will depend on type of cytopaenia accompanied.
How do we treat aplastic anaemia?
Transfusion, antibiotics, iron chelation.
Which is the most common inherited aplastic anaemia?
Fanconi anaemia (fanconi syndrome is different - a renal problem).
Give an example of a myeloproliferative disorder.
Chronic myeloid leukaemia (CML)
Give one philadelphia chromosome positive and one philadelphia chromosome negative myeloproliferative disorder.
One proliferative chromosome +ve = CML
One proliferative chromosome -ve = Polycythaemia vera
Which condition is philadelphia chromosome negative and associated with JAK2 mutations
Polycythaemia vera.
What is the difference between polycythaemia vera and pseudo polycythaemia vera?
Polycythaemia vera = high red cell mass, high plasma volume.
Pseudo polycythaemia vera = NORMAL RED CELL MASS, high plasma volume.
Which mutation is most associated with polycythaemia rubra vera?
JAK2 mutation.
After venesection, which medication is usually used for maintenance?
Hydroxycarbamide.
What is the name of the myeloproliferative disorder where megakaryocytes dominate the bone marrow?
Essential thrombocythaemia - 50% associated with JAK2 mutation.
How do we treat essential thrombocythaemia?
Aspirin and hydroxycarbamide.
What is the opposite to cytopenia?
Cytosis.
When do we use red cells vs. platelets vs. FFP for transfusion?
Red cells = iron deficiency/ B12/ folate deficiency
Platlets = TTP, DIC
FFP = often when a patient undergoes surgery
For all, do not transfuse unless actively bleeding.
Name one immune and one non immune immediate adverse affect to blood transfusion.
Immune = TRALI
Non immune = TACO.
delayed is more graft vs. host disease, viral infections, iron overload.
Anaphylaxis is more common in patients with what?
IgA deficiency.
Which antibodies mediate intravascular haemolysis compared with extravascular?
Intravascular haemolysis = IgM related
Extravascular haemolysis = IgG related.
Give 3 main presentations of graft Vs host disease
Skin desquamation
Diarrhoea
Liver failure
How do we differentiate between TACO and TRALI?
TACO = raised JVP (; cardiac overload).
Caseating granulomas are common of which condition?
TB
Name the main investigations in TB and what we would see.
CXR (upper lobe cavitation)
Sputum samples (microscopy on Ziehl-Neeson stain), acid fast bacilli seen
Tuberculin skin prick test
How do we treat TB? and for what time period?
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
All 4 for x2 months, then continue R+I for 4 more months.
Which medication gives orange secretions as a side effect?
Rifampicin
Which medication used to treat TB can cause optic neuritis as a side effect?
Ethambutol
Which condition is CURB 65 used for?
Pneumonia
Which are the three main pathogens which can cause pneumonia?
Streptococcus, klebsiella, pseudomonas, haemophilus.
What is the difference between typical and atypical pneumonia?
Atypical is not in keeping with CXR, does not common signs and does not respond to penicillin.
Which is the gram negative enterobacter rod which can cause pneumonia?
Klebsiella pneumonia.
Which is the most common bacteria to cause pneumonia?
Streptococcus pneumoniae.
Travel, air conditioning and pneumonia symptoms. Which bacteria is the cause?
Legionella.
Which pneumonia is associated with birds?
Chlamydia Psittaci.
Which are the three main investigations to diagnose pneumonia.
- CXR
- Sputum MC&S
- Atypical screen: Legionella, Chlamydia
Which are the bacteria to cause atypical pneumonia?
Legionella and mycoplasma.
Why do penicillins not work against atypical bacteria for TB?
No cell wall in atypical bacteria.
Which is the first line medication treatment for Hospital acquired pneumonia?
Ciprofloxacin and Vancomycin.
Where someone is allergic to penicillin, what is the first line medication?
A macrolide e.g. Clarithromycin.
or a quinolone e.g. Ciprofloxacin.
Ciprofloxacin is what kind of medication?
Quinolone
How will a moderate CURB score compare with a severe CURB score for treatment?
Moderate CURB = amoxicillin and clarithromycin
Severe CURB = Co-amoxiclav and clarithromycin
Which is the most common pathogen for infective endocarditis in IVDU?
Staphylococcus aureus.
Which is the most common pathogen for infective endocarditis prosthetic valve patients?
CoNS (coagulase negative staphylococci).
Duke’s criteria is used to diagnose which condition?
Infective Endocarditis.
Which are the 3 types of GI infections?
Secretory diarrhoea - no fever e.g. Cholera
Inflammatory diarrhoea - fever e.g. Campylobacter, Shigella
Enteric fever e.g. Yersinia
What do we treat IE with? acutely vs. subacutely?
Acutely - Flucloxacillin
Subacutely - Benzylpenicillin and gentamycin
Prosthetic valve - vancomycin and gentamycin
Which bacterium causes Pseudomembranous colitis and how do we treat it?
Clostridium difficile.
First line = Metronidazole
Second line = Vancomycin.
Which bacterium can cause sudden vomiting and non-bloody diarrhoea from reheated rice?
Bacillus Cereus (self limiting).
Traveller’s diarrhoea is caused by which bacteria and how is it treated?
E. Coli. Usually self limiting but can be treated with Ciprofloxacin.
Which is the culprit for non bloody diarrhoea after eating poultry?
Salmonella
Which is the culprit for bloody diarrhoea after eating poultry?
Campylobacter Jejuni.
Rice water stool is caused by which bacteria?
Vibrio Cholera
Which bacteria is the culprit for having had unpasteurised dairy? What is the treatment?
Listeria Monocytogenes.
Treatment: Ampicillin.
Differentiate between Norovirus, adenovirus and rotavirus.
Norovirus = Adult outbreaks Adenovirus = Secretory diarrhoea <2 years Rotavirus = Secretory diarrhoea < 6 years
Which marker is almost always indicative of a uti?
Nitrites
What is the difference between a lower and upper UTI?
Lower UTI = only bladder.
Upper UTI = Kidney infection (pyelonephritis).
Which is the most common pathogen for UTIs?
E. Coli
Which are the two positive markers in UTI?
Nitrites and leukocytes (less specific).
How do we treat UTIs?
Lower UTI = Nitrofurantoin/ Trimethoprim Upper UTI (pyelonephritis) = admit, coamoxicillin, gentamicin.
Which is the antibiotic of choice for Staphylococcus aureus at wound sites?
Flucloxacillin.
Which are the investigations of choice for septic arthritis?
Joint aspirate, MC&S, Blood cultures.
Which is the most common bacteria at prosthetic valves?
CoNS - coagulase negative staphylococci.
What does a prosthetic joint make someone at risk for?
Septic arthritis.
Clostridium difficile can cause what and is treated with which medication?
Pseudomembranous Colitis
Treated with Metronidazole.
What is a risk factor for E.Coli?
Catheters
Which are the main bacteria found at wound sites/ surgical site infection?
MRSA, CoNS (coagulase negative staphylococcus)
Which is the most common cause of meningitis?
Neisseria Meningitidis.
Streptococcus pneumoniae.
In neonates, which is the most common microorganism to cause meningitis?
Group B Streptococcus
Which bacteria is encephalitis most commonly caused by?
HSV1
Which medication do we use to cover for Listeria?
Ampicillin
How do we treat bacterial meningitis?
Resuscitate, IV ceftriaxone, corticosteroids.
How will bacteria compare with virus in terms of CSF?
Bacteria = turbid, cloudy, low glucose, polymorph cells Virus = Clear, normal glucose, mononuclear cells
What are the differentials for a painful lump vs. painless lump?
Painful lump = Syphilis
Painless lump = HSV.
What type of bacteria is Neisseria gonorrhoea?
Gram negative diplococcus.
How do we treat gonorrhoea?
Ceftriaxone IM - 250mg single dose.
Obligate intracellular gram negative pathogen. Which condition?
Chlamydia Trachomatis
How do we diagnose Chlamydia?
How do we treat Chlamydia?
NAAT - nucleic acid amplification tests.
Azithromycin 1g stat, doxycycline 100mg BD for 7 days.
What is a main complication of chlamydia?
PID.
Which bacteria causes syphilis?
Treponema pallidum
What are the signs of syphilis?
3 stages
1st stage = painless genital ulcer, 6 weeks
2nd stage = rash on palms and soles, lymphadenopathy
3rd stage = 20-30 years later: gummatous syndrome = granulomas, cardiovascular, neurological
What is gummatous disease?
Third stage syphilis i.e. tertiary syphilis where you see granulomatous lesions.
Treponema - which disease?
Syphilis.
How do we treat syphilis?
Single dose IM penicillin - doxycycline if allergic.
What is Chancroid?
A tropical ulcer disease in Africa. Diagnosed by chocolate agar.
‘Strawberry cervix’ is a cause of which bacteria and therefore which condition?
T. vaginalis protozoa
Trichomoniasis
Treat with metronidazole
What are 3 characteristics of bacterial vaginosis?
Which is the characteristic cell on microscopy?
Abnormal vaginal flora, low lactobacill, discharge, odour.
Clue cells.
Thick white cottage cheese discharge. What is the diagnosis?
Candidiasis.
Small papules as a dsDNA virus. What is the diagnosis?
Molluscum contagiosum
Genital warts are what kind of virus? Which virus subtypes are specifically common causes?
dsDNA human papillomavirus. HPV6 or HPV 11.
Name 3 viral STIs
Hepatitis
Herpes
HIV
How does Rifampicin work - what is it used to treat?
Inhibits RNA synthesis - treats TB mycobacteria
How do tetracyclines work. Give one example.
Inhibit protein synthesis. Doxycycline
Name the three beta lactam types?
Penicillins
Cephalosporins
Carbapenems
Which are the broad spectrum antibiotics?
Co-amoxiclav, ciprofloxacin.
Which are the narrow spectrum antibiotics?
Flucloxacillin, gentamicin, metronidazole.
What type of virus if influenza?
8 segments RNA genome.
Natural reservoir is ducks
Give 2 hepatic causes of pale stool colour.
Hepatic/ post hepatic causes:
- gallstones
- hepatitis
- gallstones
Why do we have no bilirubin in the urine in pre-hepatic disorders?
Bilirubin conjugation has not happened. Only conjugated bilirubin can pass into the urine. Unconjugated is bound to albumin which cannot pass through the glomerulus.
Which molecule is unconjugated bilirubin bound to?
Albumin.
What is a marker for increased haemolysis?
Raised LDH.
Give a cause of hepatomegaly with a smooth border compared to with a craggy border.
Smooth border = Viral hepatitis, biliary tract obstruction
Craggy border = PCOS, Cirrhosis
Urine colour change and abdominal pain. What enzyme deficiency could this be?
AIP - acute intermittent porphyria. (build up of porphyrins due to disruption in Hb synthesis).
In which porphyria are skin lesions seen?
HCP and VP
not AIP
Why can’t we use urine to measure protoporphyrin levels?
Protoporphyrin is lipophilic - use RBC protoporphyrin levels instead.
Which hypothalamic hormones stimulates ACTH from the pituitary?
CRH
Name one key side effect of a TRH injection.
Metallic taste in mouth.
How do we do the CPFT? Combined pituitary function test.
Fast patient overnight
Administer the hypothalamic hormones i.e. GnRH, TRH and insulin.
Measure pituitary hormones (GH, TSH, LH, FSH, prolactin) at 0,30,60,90,120 minute intervals.
Is dopamine a hypothalamic or pituitary hormone?
Hypothalamic hormone.
Differentiate between mild, moderate and extreme elevation in high prolactin levels.
Mild = <1000miu/l (stress, recent breast exam, PCOS) Moderate = 1000-5000 miu/l (hypothalamic tumour, drugs) Extreme = >5000 miu/l (macroprolactinoma)
What is the figure for high prolactin?
> 5000 miu/l
How do we treat prolactinoma?
- Dopamine agonist = cabergoline, bromocriptine
2. transphenoidal excision
What is the gold standard for acromegaly?
OGTT
Is Hashimoto’s hyperthyroidism or hypothyroidism?
Hypothyroidism
Give 3 differentials for high thyroxine.
Grave’s disease
Plummer’s (toxic multinodular goitre)
Drugs e.g. amiodarone.
Are Grave’s and plummer’s painful or painless goitres?
Painless
What is MEN?
Multiple endocrine neoplasia = gives a predisposition to developing endocrine cancers
MEN1
MEN2a
MEN2b
Calcium is bound to which molecule?
50% bound to albumin - so calcium is affected by albumin level.
45% ionised (free)
What do Vitamin D levels look like in primary, secondary and tertiary hyperparathyroidism?
Normal
Calcium is bound to which molecule when not ionised?
Albumin
Which is the main marker of dehydration?
urea
Trousseau’s and Chvostek’s sign are seen in which condition?
Hypocalcaemia
Give one cause of low calcium with high phosphate vs. low calcium with low phosphate.
Low calcium, high phosphate: hypoparathyroidism
Low calcium, low phosphate:
osteomalacia.
How do we differentiate between liver and bone ALP?
Liver ALP will also show a rise in gamma-GT.
Write down the order of lipoproteins in order of density.
Chylomicron < FFA < VLDL < IDL < LDL < HDL
What is the mechanism of statins?
HMG-CoA reductase inhibitor
Which is the receptor for LDLs?
PCSK9
How does Orlistat work?
Gut lipase inhibitor
The Guthrie blood test is done at which age and for which condition?
6 days old for Cystic Fibrosis
What is MELAS?
Mitochondrial encephalopathy lactic acidosis stroke like episodes.
What is a fasting glucose value diagnostic for Diabetes Mellitus for?
> 7mmol/L
What will we see in Diabetic ketoacidosis?
Confusion
Kussmaul breathing
Abdominal pain, N+V.
In fluid replacement, how much saline do we usually give?
0.9% saline over 1hr.
What is HHS?
Hyperosmolar hyperglycaemic state
pH >7.3
High blood glucose, high osmolarity.
When may we see low glucose and low insulin?
Non-islet tumour hyperglycaemia
Tumours which secrete IGF2 = binds to IGF1 and insulin receptor
Which is the marker of insulin?
C Peptide
What is the more common type of hyperbilirubinaemia in infancy?
High Conjugated bilirubin
What are the different causes of neonatal jaundice and at which stages?
Jaundice within the 1st 24 hours of life = acute haemolysis/ sepsis
Jaundice after 2 weeks = hepatobiliary failure
Which is the gold standard to measure GFR?
Inulin
When will we see casts in urine microscopy?
Glomerulonephritis
How do we define Acute kidney injury?
Serum creatine > 26 within 48 hours.
>50% rise in serum creatine over 7 da7s
Give 5 indications for dialysis.
Acidosis Electrolyte disturbance Intoxication e.g. lithium, aspirin Overload fluid e.g. pulmonary oedema Uraemic encephalopathy
AEIOU
What is the GFR for end-stage kidney failure?
<15
Which is the biggest cause of mortality in CKD?
Vascular calcification
What is the difference between haemodialysis and peritoneal dialysis?
Haemodialysis = insert arteriovenous fistula
Peritoneal dialysis = Uses peritoneum as dialysis membrane
Rutherford Morrison (hockey stick scar) is for which condition and in which location?
Kidney transplant in right iliac fossa
The mesangial cell is the macrophage of which organ?
Kidney
Give an example of a PAMP
Bacterial sugar, DNA, RNA
Which cells express inhibitory receptors to prevent inappropriate activation against self molecules?
Natural killer cells.
What will define an altered self cell? i.e. potential pathogen?
Those which lack inhibitory signals.
Name the 3 secondary lymphoid organs.
Lymph nodes
Spleen
MALT - mucosal associated lymphoid tissue.
Describe the process of T cell maturation
T cells exported from haematopoetic stem cells to the thymus to undergo positive and negative selection. Mature T cells move to secondary lymphoid organs e.g. spleen
Which receptor do all T cells express?
CD3+
Which are the cytotoxic T cells?
CD8+ T cells
What is central tolerance?
No recognition of self antigens = cell can survive.
The classical pathway involves which complements?
C1, C2, C4
The MBL pathway involves which complements?
C2, C4.
What is the difference between cytokines and chemokines?
Cytokines e.g. IL-2, IL-6 etc.
Chemokines = CCL19, CCL21
Which antibody is found in respiratory and GI secretions?
IgA.
What is Kostmann syndrome?
Failure of neutrophil maturation
Which is the mutation for neutropenia?
ELA-2 - neutrophil elastase.
What is NBT? Where can we use it?
Nitro-blue tetrazolium
A dye which changes colour from yellow to blue when there is H202 free radical interaction.
Chronic granulomatous disease.
Which complements are involved in the mannose binding lectin pathway?
C2 and C4, not C1.
The classical, alternate and MBL pathway all converge onto which complement?
C3
Which mutation causes x-linked SCID?
Mutation of gamma chain of IL-2 receptor on chromosome 13.
Which mutation causes x-linked SCID?
Mutation of gamma chain of IL-2 receptor on chromosome 13.
Which disease is caused by 22q11.2 deletion?
DiGeorge syndrome. Reduced T cell number, normal B cell number.
Give the factors of DiGeorge syndrome.
CATCH 22 Cardiac abnormalities Abnormal faces (high forehead, low ears) Thymic aplasia Cleft palate Hypocalcaemia
chromosome 22
What is NBT? When may we use it?
A dye which changes from colour to yellow to blue following interaction with hydrogen peroxide.
Chronic granulomatous disease.
How do we differentiate between the complement deficiencies?
CH50 and AP50 tests.
e.g. SLE has low CH50, low C3 and C4.
C1q deficiency has low CH50, C3 and C4.
Give 3 tests to investigate lymphocyte deficiencies.
- White cell count
- Lymphocyte subsets
- IGs
Which type of immunity is involved in autoinflammatory responses?
Innate - adaptive is autoimmune
How can we class autoinflammatory or autoimmune diseases?
Monogenic or polygenic.
Autoinflammatory or autoimmune.
What type of disease are Crohn’s and UC?
Polygenic autoinflammatory.
What type of disease is rheumatoid arthritis?
Polygenic autoimmune disease
Give an example of a mixed pattern disease
Ankylosing spondylitis
How would you classify pernicious anaemia as a disease?
Polygenic autoimmune disease.
Monogenic autoinflammatory diseases have an issue which type of immunity?
Innate immunity
What is familial mediterranean fever? mutation, recessive or dominant? which cell type affected?
Autosomal recessive
Mutation in MEFV
Gene encodes pyrin-marenostrin - expressed by neutrophils.
So, in familial mediterranean fever = neutrophil issue
Can
Colchicine is associated with treating what type of conditions? Give 2 examples.
Inflammatory conditions. e.g. gout, familial mediterranean fever.
What will a mutation in the FAS pathway cause?
Failure of lymphocyte apoptosis.
What is tolerance?
Control of not producing an immune response to an antigen.
‘i can be tolerant, i can have them around and do nothing’.
Where is a FAS pathway mutation seen?
ALPS - autoimmune lymphoproliferative syndrome.
What is APS1?
Autoimmune polyendocrine syndrome type 1
= abnormality in tolerance.
Defect in AIRE. - autoimmune regulator gene. AIRE is involved in T cell tolerance.
Addisons and Vitiligo are seen in which monogenic autoimmune disease?
APS1 - autoimmune polyendocrine syndrome 1.
Where are HLA associations more common - autoimmune or autoinflammatory conditions?
Autoimmune
HLA-DR4 is associated with which condition?
Rheumatoid arthritis.
HLA B27 is associated with which diseases?
Ankylosing spondylitis, reactive arthritis, IBD.
Type I hypersensitive disorders are which Ig related?
IgE
Give 2 examples of IgE mediated allergies vs. Non-IgE mediated.
IgE = Peanuts, penicillin, latex
Non IgE = Exercise, NSAIDS, Opioids.
How do we manage anaphylaxis?
elevate legs, 100% oxygen, IV adrenaline 500mcg, hydrocortisone 200mg IV.
bowed legs. specifically which diagnosis?
Paget’s disease
High paraprotein. specifically which diagnosis?
Multiple myeloma
Is Rheumatoid arthritis symmetrical or asymmetrical?
Symmetrical
Petechical rash after a URTI. What is the diagnosis?
ITP.
Which virus increases the risk of nasopharyngeal cancer?
EBV
