Final Review Flashcards
Which of the following nail deformities is most associated with Psoriasis?
Clubbing
1
Koilonychia
2
Splinter Haemorrhage
3
Beau’s Lines
4
Nail Pitting
5
Which of the following nail deformities is most associated with Psoriasis?
Clubbing
1
Koilonychia
2
Splinter Haemorrhage
3
Beau’s Lines
4
Nail Pitting
5
Dx? [1]
Tx - if non severe? [4] or severe? [2]
top: trophozoite infecting a reticulocyte
bottom: trophozoite infecting an RBC with Schuffner’s dots (eosinophilic) with preserved cell morphology
suggestive of plasmodium vivax - similar to ovale but without RBC shape change
treated with **oral artemeter + lumefantrine or quinine sulphate or doxycyline **
consider artesunate + quinine dihydrochloride IV if severe infection
Dx
classic findings associated with plasmodium malariae which only affects senescent RBCs
What is the most common primary immunodeficiency syndrome? [1]
Selective IgA deficiency
Defect in moving material into lysosomes X Giant granules = ?
Defect in moving material into lysosomes x Giant granules = ?
Chediak-higashi syndrome
For symptomatic classical CGD the mainstay of treatment is []
For symptomatic classical CGD the mainstay of treatment is definitive correction i.e. HSCT
Name 3 x-linked dominant diseases [3]
retinitis pigmentosa
chrondrodysplasia
alport syndrome (type IV collagen gene defect)
What is the definition of incidence?
Incidence = number of new cases (or deaths) of a disease per 100,000 people per year
Describe the pathophysiology of Fragile-X syndrome
Fragile X syndrome is caused by a mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome.
The FMR1 gene codes for the fragile X mental retardation protein, which plays a role in cognitive development in the brain.
Long ears; thin face
Describe the inheritence of Fragile-X mental retardation [1]
It is X-linked dominant
Males are always affected, but females can vary in how much they are affected.
This is because females have a spare normal copy of the FMR1 gene on their other X chromosome.
Describe the features of Fragile X syndrome in males and females
Features in males
* learning difficulties
* large low set ears, long thin face, high arched palate
* macroorchidism
* hypotonia
* autism is more common
* mitral valve prolapse
Features in females (who have one fragile chromosome and one normal X chromosome)
* range from normal to mild
What is the inheritence pattern of Hypophosphatamic rickets? [1]
Hereditary hypophosphataemic rickets.
- The most common form is x-linked dominant, however it also has other modes of inheritance.
- There is a rare form of rickets caused by genetic defects that result in low phosphate in the blood
Describe the pathophysiology of X-linked dominant-Hypophosphatamic rickets [3]
- Suggested that the phosphate regulating endopeptidase X-linked (PHEX) enzyme regulates fibroblast growth factor 23 (FGF23).
- This protein normally inhibits the kidneys’ ability to reabsorb phosphate into the bloodstream.
- There is an increase of FGF23 in patients but no direct link yet between the proteins.
Describe how APP and PSEN genes contribute to AD pathophysiology [2]
APP: when cleaved by B & Y secretases get ABP - accumulates to cause amyloid plaques in brain
PSEN [1&2] function as part of the complex the cleaves in the y site - so if have hyperfunction of PSEN then causes AD
Name a gene that has been found to be a suppressor gene for AD [1]
BACE2
Describe the features of:
* Trisomy 13 (Patau’s syndrome)
* Trisomy 18 (Edwards syndrome)
Trisomy 13 (Patau’s syndrome):
* Microcephalic, small eyes
* Cleft lip/palate
* Polydactyly
* Scalp lesions
Trisomy 18 (Edwards syndrome):
* Micrognathia
* Low-set ears
* Rocker bottom feet
* Overlapping of fingers
47, XXY refers to which sex chromosome aneuploidy? [1]
Describe the features of this syndrome [+]
47, XXY: Klinefelter syndrome
* Taller height
* Wider hips
* Gynaecomastia
* Weaker muscles
* Small testicles
* Reduced libido
* Shyness
* Infertility
* Subtle learning difficulties (particularly affecting speech and language)
Describe the pathophysiology of Rieger syndrome [1]
A deletion of REIG gene from chromosome 4
When gene gets moved to chromosome 12, becomes less active (and acts like a deletion)
Iris of the eye fails to develop - may lead to blindness later in life
- typically develop raised intra-ocular pressure and glaucoma
What is the genetic and pathophysiological features of Tay-Sachs? [3]
Tay-Sachs disease is caused by mutations in the HEXA gene located on chromosome 15
- causes progressive damage to the nerve cells, particularly neurons in the brain, causing the characteristic neurological symptoms of the disease
- Tay-Sachs disease follows an autosomal recessive pattern of inheritance
- Symptoms of Tay-Sachs disease typically manifest in early infancy, usually around 3 to 6 months of age.
What is the genetic and pathophysiological features of achondroplasia? [3]
Achondroplasia is an autosomal dominant disorder associated with short stature. It is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene. This results in abnormal cartilage giving rise to:
* short limbs (rhizomelia) with shortened fingers (brachydactyly)
* large head with frontal bossing and narrow foramen magnum
* midface hypoplasia with a flattened nasal bridge
* ‘trident’ hands
* lumbar lordosis
In most cases (approximately 70%) it occurs as a sporadic mutation. The main risk factor is advancing parental age at the time of conception. Once present it is typically inherited in an autosomal dominant fashion.
Retinitis pigmentosa primarily affects [] cells in the retina, particularly [], which are responsible for peripheral and night vision.
Retinitis pigmentosa primarily affects photoreceptor cells in the retina, particularly rods, which are responsible for peripheral and night vision.
What are the features of Retinitis pigmentosa? [3]
Features
* night blindness is often the initial sign
* tunnel vision due to loss of the peripheral retina (occasionally referred to as funnel vision)
* fundoscopy: black bone spicule-shaped pigmentation in the peripheral retina, mottling of the retinal pigment epithelium
Describe the genetic and pathophysiology of PKU [4]
Phenylketonuria (PKU) is an autosomal recessive condition caused by a disorder of phenylalanine metabolism.
This is usually due to defect in phenylalanine hydroxylase, an enzyme which converts phenylalanine to tyrosine.
In a small number of cases the underlying defect is a deficiency of the tetrahydrobiopterin-deficient cofactor
The gene for phenylalanine hydroxylase is located on chromosome 12
How do patients of PKU present? [5]
The consequences of PKU include:
* usually presents by 6 months e.g. with developmental delay
* child classically has fair hair and blue eyes
* learning difficulties
* seizures, typically infantile spasms
* eczema
* ‘musty’ odour to urine and sweat
If you find S. aureus as a cause of UTI - what other pathology would you have a suspicion of? [1]
S. aureus isn’t usual uropathogen - have suspicion for endocarditis
- endocarditis -> renal abscess -> urine
What are the general principles for CAP:
- Low severity [1]
- Moderate severity [2]
- High severity [3]
Low severity
- single antibiotic
Moderate severity:
- amoxicillin & a macrolide (azithromycin, clarithromycin, and erythromycin)
High severity
- β-lactamase stable β-lactam (e.g. co-amox) & a macrolide
A patient presents with CAP - under what conditions would you give pip-taz? [3]
If they have pseudomonas infection:
-CF; bronchiectasis
How do you differentiate between the symptoms of meningitis and encephaltiis?
Meningitis
- Symptoms of headache, neck stiffness & photophobia
Encephalitis:
- Symptoms associated with altered cerebral function (e..g Seizures, weakness, behaviour change, drop in GCS etc)
What are the implications of dinstinction betwen mengintis vs encephalitis with regards to treatment? [2]
Likely causes e.g. in UK encephalitis viral > bacterial
Treatment e.g. viral meningitis does NOT need treatment, enceph DOES
Under what conditions would you suspect Streptococcus gallolyticus causing infective endocarditis? [1]
Due to GI malignancy
What are the three most common causes of viral meningitis? [3]
Enteroviruses (e.g., coxsackievirus)
Herpes simplex virus (HSV)
Varicella zoster virus (VZV)
What does a non-blanching rash indicate with meningitis? [1]
Where there is meningococcal septicaemia, children can present with a non-blanching rash. Other causes of bacterial meningitis do not usually cause the non-blanching rash.
Typical antibiotics are to treat bacterial meningitis include
Under 3 months – [] plus [] ([] is to cover listeria)
Above 3 months – []
PLUS
[]
Typical antibiotics are:
Under 3 months – cefotaxime plus amoxicillin (amoxicillin is to cover listeria)
Above 3 months – ceftriaxone
PLUS
Steroids (e.g., dexamethasone) are also used in bacterial meningitis to reduce the frequency and severity of hearing loss and neurological complications.
When treating bacterial meningitis - what drug should be given if suspect penicillin-resistant pneumococcal infection? [1]
Vancomycin should be added if there is a risk of penicillin-resistant pneumococcal infection (e.g., recent foreign travel or prolonged antibiotic exposure).
What is the protocal for pregnant patients if they are < 28 weeks and have a primary attack of HSV? [1]
elective caesarean section at term is advised if a primary attack of herpes occurs during pregnancy at greater than 28 weeks gestation
Passmed:
- elective caesarean section at term is advised if a primary attack of herpes occurs during pregnancy at greater than 28 weeks gestation
women with recurrent herpes who are pregnant should be treated with suppressive therapy and be advised that the risk of transmission to their baby is low
Primary genital herpes contracted before [] weeks gestation is treated with [] during the initial infection.
This is followed by regular prophylactic [] starting from 36 weeks gestation onwards to reduce the risk of genital lesions during labour and delivery.
Primary genital herpes contracted before 28 weeks gestation is treated with aciclovir during the initial infection.
This is followed by regular prophylactic aciclovir starting from 36 weeks gestation onwards to reduce the risk of genital lesions during labour and delivery.
Recurrent genital herpes in pregnancy, where the woman is known to have genital herpes before the pregnancy, carries a low risk of neonatal infection (0-3%), even if the lesions are present during delivery.
Regular prophylactic [] is considered from [] weeks gestation to reduce the risk of symptoms at the time of delivery.
Recurrent genital herpes in pregnancy, where the woman is known to have genital herpes before the pregnancy, carries a low risk of neonatal infection (0-3%), even if the lesions are present during delivery.
Regular prophylactic aciclovir is considered from 36 weeks gestation to reduce the risk of symptoms at the time of delivery.
HSV
After an initial infection, the virus becomes latent in the associated [].
Typically this is the [] with cold sores and the sacral nerve ganglia with genital herpes.
. After an initial infection, the virus becomes latent in the associated sensory nerve ganglia.
Typically this is the trigeminal nerve ganglion with cold sores and the sacral nerve ganglia with genital herpes.
What is the name for this complication of HSV? [1]
herpes keratitis
State 5 complications of VZV infection [5]
- A common complication is secondary bacterial infection of the lesions
- pneumonia
- encephalitis (cerebellar involvement may be seen)
- disseminated haemorrhagic chickenpox
- arthritis, nephritis and pancreatitis may very rarely be seen
VZV infection
immunocompromised patients and newborns with peripartum exposure should [].
If chickenpox develops then [] should be considered
immunocompromised patients and newborns with peripartum exposure should receive varicella zoster immunoglobulin (VZIG).
If chickenpox develops then IV aciclovir should be considered
How does VZV specifically cause disease? [1]
Inhibits viral DNA polymerase.
Acylcvir toxicity can cause what syndrome? [1]
Describe it x
Cotard syndrome.:
- rare mental disorder in which the affected person holds the delusional belief that they are dead, do not exist, are putrefying, or have lost their blood or internal organs
What are three key manifestations of CMV in IC patients? [3]
Retinitis
Pneumonitis
Oesphagitis
How do you manage CMV:
- prophylactically
- pre-emptive therapy
Prophylactically:
- ARV use after transplant to bridge period with highest risk
Pre-emptive therapy:
- monitor CMV activity after transplant and start ARV at first indication of active CMV replication (because tx can suppress bone marrow - so you dont want to do this if not needed)
Describe how CMV retinitis presents [1]
Which patient population? [1]
common in HIV patients with a low CD4 count (< 50)
presents with visual impairment e.g. ‘blurred vision’. Fundoscopy shows retinal haemorrhages and necrosis, often called ‘pizza’ retina
Describe the two main complications of EBV in IC patients [2]
Post Transplant Lymphoproliferative Disorder (PTLD)
* Usually first year post transplant
* 3- 10% of patients post SOT
* 40 – 60% mortality
Lymphoma - NHL in transplant patients, also common in HIV patients
What are the risk factors for Post Transplant Lymphoproliferative Disorder (PTLD) [5]
- EBV seronegative prior to transplant i.e. associated with primary infection
- Children < 5 years
- Antirejection therapy(OKT3 or ATG)
- CMV seromismatch
- Type of transplant
Which type of transplant is most likely to have Post Transplant Lymphoproliferative Disorder (PTLD) in EBV infection?
Heart/lung, lung, pancreatic-renal
Small bowel
Heart, liver
Renal, bone marrow
Which type of transplant is most likely to have Post Transplant Lymphoproliferative Disorder (PTLD) in EBV infection?
Heart/lung, lung, pancreatic-renal
Small bowel
Heart, liver
Renal, bone marrow
Describe the symptoms of PTLD EBV [5]
- Unexplained fever
- GI upset
- Lymphadenopathy - retroperitnoneal
- Tonsillar hypertrophy
- IM
- Hepatic /splenic enlargement
- Anaemia/pancytopenia
- Graft dysfunction
What is a main stay treatment for PTLD? [1]
Rituximab
How does adenovirus present in healthy people [3] and IC people [6]
Healthy people:
* Respiratory disease (usually mild and self-limiting)
* Keratoconjunctivitis
* Gastroenteritis
Immunosuppressed:
* pneumonia
* hepatitis
* haemorrhagic cystitis
* enterocolitis
* encephalitis
* disseminated infection
State the risk factors for adenovirus disease in transplant patients [4]
Children»_space; adults;
severe GVHD
cord blood transplant,
alemtuzumab conditioning;
liver, heart, multivisceral SOT
How do you detect adenovirus in immunosuppressed? [2]
What should you do if test postive in ^? [1]
Screening via blood & urine PCR
If positive - test at other sites including resp & stool
How do you treat adenovirus in IC? [1]
Brincidofovir (or reduce level of immunosuppression)
Name two polyomaviruses that are cirtical in IC [2]
JC virus and BK virus
Describe life cycle of JC virus and BK virus [2]
Initial viraemia and seeding of kidney –> latency
Reactivation: viruria –> viraemia –> end-organ disease
Describe the three main syndromes with of JC and BK viruses [3]
BK virus-associated haemorrhagic cystitis (usually allogeneic HSCT recipients)
BK virus-associated nephropathy (BVAN, renal transplant recipients)
JC-PML
How do you detect COVID-19? [1]
Detection of viral RNA viral by PCR
Nasopharyngeal swab
How do you treat COVID (in normal patients):
- Moderate infection [1]
- Severe infection [3]
Mild-mod: conservative
Hospital: dexamethasone + remdesivir
(nucleotide analogue), CPAP
What calculation do you use when you’re investigating the liklihood of developing a chronic disease between two groups? [1]
Relative risk
Vancomycin-Resistant Enterococci (VRE) - what can you use instead [1]
first line – glycopeptides, such as vancomycin (but not for VRE or vancomycin-resistant S. aureus [VRSA]) or teicoplanin, which are narrow-spectrum agents, only available IV that cannot penetrate the blood–brain barrier as they are large molecules; vancomycin is nephrotoxic so levels need to be measured
for VRE – treat with oxazolidinone (eg. linezolid, which has excellent penetration into skin and brain; however, it can cause bone marrow suppression, peripheral neuropathy and optic neuritis)
other options: daptomycin, tigecycline
Describe the relation between HLAs and HIV
- What does HIV bind to? [3]
- HIV binds to CD4 and CCR5 of CXCR4
- Long term non-progressors: suppress viral loads to undetectable levels with elevated CD4 T cell counts in the abscence of ART
- The two main HLA molecules: HLA-B2705 or HLAB5701 cause this adapted response
Which HLA is associated with ankylosing spond? [1]
HLA-B27
Describe the direct pathway to alloantigen presentation in transplantation
- Donor APCs migrate from graft to secondary lymphoid organs in host.
- Present MHC to recipient T cells which become activated
- They go back to the graft and cause damage ):
Describe the indirect pathway for alloantigen presentation in tranplantation
- Recipient APCs go to graft, phagocytose a donor peptide and put on MHC
- Activate T cells in secondary lymphoid organs
Describe why an acute rejection of a graft occurs [2]
2-3 weeks after
Driven by direct pathway of allorecognition - alloreactive T cells infiltrate graft and cause tissue death
Causes parenchymal cell damage & interstitial inflammation
Describe the process of chronic graft rejection [1]
Driven by indirect pathway of allorecognition - alloreactive T cells and antibodies infiltrate graft - occlusion of blood vessels and fibrosis
When perfoming a clinical exam of a person with muscular dystrophy (like DMD), what would you particularly look out for? [6]
Gower’s sign
- the child climbs up their legs when rising from the floor
Weakness:
- typically the proximal and distal leg muscles in the earlier phases of the disease.
Calf pseudohypertrophy:
- due to the accumulation of connective tissue and fat replacing muscle tissue.
Waddling gait:
- typically exacerbated when attempting to run.
Tip-toe walking
- occurs due to shortening of the Achilles tendon.
Loss of the arches of the feet (i.e. flat feet)
Difficulty or inability to squat
TOM TIP: [] sign is a favourite in exams.
If there is a 5 year old boy presenting with vague symptoms of muscle weakness and the description is that you notice them [] to stand up, the answer is probably Duchennes muscular dystrophy.
They may ask “what is the underlying genetic inheritance of the most likely cause?” The answer is []
TOM TIP: Gower’s sign is a favourite in exams.
If there is a 5 year old boy presenting with vague symptoms of muscle weakness and the description is that you notice them using their hands on their legs to help them stand up, the answer is probably Duchennes muscular dystrophy. They may ask “what is the underlying genetic inheritance of the most likely cause?” The answer is X-linked recessive.
Describe the pathophysiological differences between Duchenne and Becker’s MD [1]
Duchenne muscular dystrophy
- there is a frameshift mutation resulting in one or both of the binding sites are lost leading to a severe form
Becker muscular dystrophy
- there is a non-frameshift insertion in the dystrophin gene resulting in both binding sites being preserved leading to a milder form
Describe the sweat test used to diagnose CF [3]
- A patch of skin is chosen for the test, typically on the arm or leg.
- Pilocarpine is applied to the skin on this patch.
- Electrodes are placed either side of the patch and a small current is passed between the electrodes
- This causes the skin to sweat.
- The sweat is absorbed with lab issued gauze or filter paper and sent to the lab for testing for the chloride concentration.
- The diagnostic chloride concentration for cystic fibrosis is more than 60mmol/l.
Diabetes mellitus
Autosomal recessive
Nasal polyps
Chromosome 7
Rectal prolapse
Name two anti-biotics that have the greatest spectrum in coverage
Meropenum/Imipenem
Piperacillin-Tazobactam
Cefrtiaxone
Cefuroxime
Name two antibiotics that work purely as gram positive coverage [2]
Vancomycin/Teicoplanin
Flucloxacillin
Benzyl Penicllin
Describe co-amoxiclav’s coverage [1]
Mostly gram+ve, with a bit of gram -ve
You treat a 20 year old who came in to the GP with vague infective symptoms.
The next day she comes back and presents with this rash.
Investigations reveal she has EBV.
Which abx was initially given?
Metronidazole
Flucoxacillin
Rifampicin
Fluroquinolone
Amoxicillin
You treat a 20 year old who came in to the GP with vague infective symptoms.
The next day she comes back and presents with this rash.
Investigations reveal she has EBV.
Which abx was initially given?
Amoxicillin
- causes a reaction with EBV infection
Primary immunodeficiency disorders
Bloody diarrhea, may be the first symptom. Eczema also develops at an early age.
Wiskott-Aldrich Syndrome
Which primary immunodeficiency disorder can you test with nitroblue tetrazolium? [1]
What would indicate that this disorder is occurring? [1]
chronic granulamatous disorder
Describe what zero order kinetics means [1]
Zero order kinetics describes metabolism which is
independent of the conc of the reactant.
Ptx presents after starting an Abx.
They complain their teeth have been stained after initiating the treatment.
What is the most likely class of Abx used? [1]
Tetracyclines
How does a patient with Leptospirosis present? [3]
Jaundice, conjunctival suffusion,
hepatorenal impairment
chloroquine
every 48hrs
most common type of non-falciparum malaria
