Miscellaneous 2 Flashcards
Chemotherapy
Give an example of alkylating agent
Give 2 examples of cytotoxic antibiotics
Give 4 examples of antimetabolites
Give 2 examples that act on microtubules
Give 1 example of irinotecan
- Alkylating agent - cyclophosphamide
- Cytotoxic abs - bleomycin, doxorubicin
- Antimetabolites - methotrexate, 5FU, 6-mercaptopurine, cytarabine
- Microtubular action- vincristine, docetaxel
- Topoisomerase inhibitor - irinotecan
CYCLOPHOSPHAMIDE
MOA
SE [3]
Alkylating agent - causes cross-linking in DNA
Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma
Bleomycin
MOA
SE
Bleomycin
MOA -degrades preformed DNA
SE- lung fibrosis
Anthracyclines - doxorubicin
MOA
SE
- Stablilise DNA-topoisomerase II complex inhibits DNA & RNA synthesis
- SE: cardiomyopathy
Antimetabolites
- Methotrexate - inhibits dihydrofolate reductase and thymidylate synthesis
- 5-FU - pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase
- 6-mercaptopurine - purine analogue
- Cytarabine - pyrimidine antagonist, myelosuppression
Acts on microtubules
Vincristine
- Vincristine inhibits formation of microtubule
- Side effects - peripheral neuropathy reversible, paralytic ileus
Docetaxel
- Prevents microtubule depolymerisation and disassebly, decreasing free tubulin
- Neutropaenia
Topoisomerase inhibitors
- Irinotecan - inhibits topoisomerase I which prevents relaxation of supercoiled DNA - myelosuppression
Cisplatin
MOA
SE
MOA - causes cross linking in DNA
SE - peripheral neuropathy, hypoMg
What is the action of IL-1, and what are its main sources?
IL-1 is produced by macrophages. Its main functions include inducing acute inflammation and fever.
What is the action of IL-2, and what are its main sources?
IL-2 is produced by Th1 cells. It stimulates the growth and differentiation of T cell responses.
What is the action of IL-3, and what are its main sources?
IL-3 is produced by activated T helper cells. It stimulates the differentiation and proliferation of myeloid progenitor cells.
What is the action of IL-4, and what are its main sources?
IL-4 is produced by Th2 cells. It stimulates the proliferation and differentiation of B cells.
What is the action of IL-5, and what are its main sources?
IL-5 is produced by Th2 cells. Its main function is to stimulate the production of eosinophils.
What is the action of IL-6, and what are its main sources?
IL-6 is produced by macrophages and Th2 cells. It stimulates the differentiation of B cells and induces fever.
What is the action of IL-8, and what are its main sources?
IL-8 is produced by macrophages. It is involved in neutrophil chemotaxis.
What is the action of IL-10, and what are its main sources?
IL-10 is produced by Th2 cells. It inhibits Th1 cytokine production and is known as an ‘anti-inflammatory’ cytokine.
What is the action of IL-12, and what are its main sources?
IL-12 is produced by dendritic cells, macrophages, and B cells. It activates NK cells and stimulates the differentiation of naive T cells into Th1 cells.
What is the action of TNF-α, and what are its main sources?
TNF-α is produced by macrophages. It induces fever and neutrophil chemotaxis.
What is the action of IFN-γ, and what are its main sources?
IFN-γ is produced by Th1 cells. It activates macrophages.
Monitoring of hereditary angioedema
associated with low plasma levels of the C1 inhibitor
- MOA - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.
- C1-INH level is low during an attack
- Low C2 and C4 levels are seen, even between attacks.
Serum C4 is the most reliable and widely used screening tool
Hereditary angioedema
Presenation
Management acute
Symptoms
attacks may be proceeded by painful macular rash
painless, non-pruritic swelling of subcutaneous/submucosal tissues
may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema)
urticaria is not usually a feature
Management
acute
HAE does not respond to adrenaline, antihistamines, or glucocorticoids
IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available
HOCM management
Management
* Amiodarone
* Beta-blockers or verapamil for symptoms
* Cardioverter defibrillator
* Dual chamber pacemaker
* Endocarditis prophylaxis
Drugs to avoid
* nitrates
* ACE-inhibitors
* inotropes
Complement deficiencies
C1 inhibitor protein deficiency
causes hereditary angioedema
C1-INH is a multifunctional serine protease inhibitor
probable mechanism is uncontrolled release of bradykinin resulting in oedema of tissues
What is c1q, c1rs, c2, c4 deficiency
predisposes to immune complex disease
e.g. SLE, Henoch-Schonlein Purpura
What does C3 complement deficiency cause?
Recurrent bacterial infections
What does C5 deficiency cause?
predisposes to Leiner disease
recurrent diarrhoea, wasting and seborrhoeic dermatitis
What does C5-9 deficiency cause?
encodes the membrane attack complex (MAC)
particularly prone to Neisseria meningitidis infection
Primary immunodeficiency
Neutrophil disorders (name 3)
B-cell disorders (name 3)
Name 1 T-cell genetic disorder
Name some 4 combined B- and T- cell disorders
Neutrophil disorders
* Chronic granulomatous disease
* Chediak-Higashi syndrome
* Leukocyte adhesion deficiency
B- cell disorders
* CVID
* Brutons congenital agammaglobulinaemia
T-cell genetic disorder
* Digeorge syndrome
Combined B-cell and T-cell disorder
* Severe combined immunodeficiency
* Ataxic telangiectasia
* Wiskott-Aldrich syndrome
* Hyper IgM syndromes
Chronic granulomatous disease
Underlying defect
Clinical manifestation
Underlying defect
* Lack of NADPH oxidase reduces ability of phagocytes to produce ROS
Clinical manifestation
* Recurrent pneumonias and abscesses
* Catalase-positive staph aureus and fungi
Chediak Higashi syndrome
Underlying defect
Clinical manifestation
Underlying defect
* Microtubule polymerization defect leading to decrease in phagocytosis
Clinical manifestation
* Affected children have ‘partial albinism’ and peripheral neuropathy.
* Recurrent bacterial infections are seen
Giant granules in neutrophils and platelets
Leukocyte adhesion deficiency
Underlying defect
Clinical manifestation
Underlying defect
* Defect of LFA-1 integrin (CD18) protein on neutrophils
Clinical manifestation
Recurrent bacterial infections.
Delay in umbilical cord sloughing may be seen
* Absence of neutrophils/pus at sites of infection
B-cell disorders
CVID
Underlying defect
Clinical manifestation
Increases risk of…
CVID
* No specific underlying genetic defect
* Low antibody levels specifically Ig types IgG, IgM, IgA
* Recurrent chest infections
* Predispose to autoimmune disorders & lymphoma
Brutons congenital agammaglobulinemia
Underlying defect
Clinical manifestations
Underlying defect
* Defect in Bruton’s tyrosine kinase (BTK) gene that leads to a severe block in B cell development
Clinical manifestations
* X-linked recessive.
* Recurrent bacterial infections are seen
* Absence of B-cells with reduced immunoglogulins of all classes
Selective IgA deficiency
Underlying defect
Clinical manifestations
Underlying defect
* Maturation defect in B cells
Clinical manifestations
* Most common primary antibody deficiency.
* Recurrent sinus and respiratory infections
* Associated with coeliac disease and may cause false negative coeliac antibody screen
* Severe reactions to blood transfusions may occur (anti-IgA antibodies → analphylaxis)
How does DiGeorge immunodeficiency manifest?
Recurrent viral or fungal diseases
Severe combined immunodeficiency
What is the most common genetic defect?
How is it inherited?
Clinical manifestation
Most common due to defect in the common gamma chain, a protein used in the receptors for IL-2 and other interleukins.
X-linked disease.
Clinical manifestation
* Recurrent infections due to virus, bacteria, fungi.
Ataxic telangiectasia
Defect
Clinical manifestation
Inheritance pattern
Features
Defect
* Defect in DNA repair enzymes
Inherited pattern - AR
Features
* cerebellar ataxia, telangiectasia (spider angiomas)
* recurrent chest infections
* 10% risk of developing malignancy, lymphoma or leukaemia
Hyper IgM syndromes
Mutation
Features
Mutation
* CD40 gene
Features
* Infection/ pneumocystis pneumonia
* Hepatitis
* Diarrhoea
Water deprivation test & post- DDAVP test
What is the diagnosis if
Urine osmolality after water deprivation remains <300
Post desmopressin test, the urine osmolality is >600
Cranial DI
Water deprivation test & post- DDAVP test
What is the diagnosis if urine osmolality after water deprivation is <300
Post desmopressin is <300
Nephrogenic DI
Water deprivation test & post- DDAVP test
What is the urine osmolality result for psychogenic polydipsia for post-water deprivation and post-desmopressin
Both remain >400
Describe mitochondrial inheritance
Mitochondrial inheritance has the following characteristics:
* inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
* none of the children of an affected male will inherit the disease
* all of the children of an affected female will inherit the disease
* generally, encode rare neurological diseases
* poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy
Give 4 examples of mitochondrial inherited diseases
- Lebers optic atrophy
- MELAS -mitochondrial encephalomyopathy lactic acidosis
- MERRF- myoclonus epilepsy with ragged-red fibres
- Kearns- Sayre syndrome
Psoriasis exacerbating factors
The following factors may exacerbate psoriasis:
* trauma
* alcohol
* drugs: beta blockers, lithium, antimalarials (chloroquine and hydroxychloroquine), NSAIDs and ACE inhibitors, infliximab
* withdrawal of systemic steroids
Streptococcal infection may trigger guttate psoriasis.
Sideroblastic anaemia
Sideroblastic anaemia is a condition where red cells fail to completely form haem, whose biosynthesis takes place partly in the mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast. It may be congenital or acquired.
Causes of sideroblastic anaemia
Congenital vs acquired
Congenital cause: delta-aminolevulinate synthase-2 deficiency
Acquired causes
myelodysplasia
alcohol
lead
anti-TB medications
Sideroblastic anaemia
Investigations
FBC
Iron studies
Blood film
Blood marrow
full blood count
* hypochromic microcytic anaemia (more so in congenital)
* iron studies
* high ferritin
* high iron
* high transferrin saturation
blood film
* basophilic stippling of red blood cells
bone marrow
* Prussian blue staining will show ringed sideroblasts
Haematological malignancies- genetics
t(9;22) - Philadelphia chromosome
CML
Haematological malignancies- genetics
t(15;17)
seen in acute promyelocytic leukaemia (M3)
fusion of PML and RAR-alpha genes
t(8;14)
seen in Burkitt’s lymphoma
t(11;14)
Mantle cell lymphoma
t(14;18)
follicular lymphoma
Renal transplant infections
Over 50% of renal transplant patients have a significant infection within the first 12 months of having a renal transplant. Why do we test CMV serology?
At the time of transplant the CMV-serological status of the donor and recipient are noted. The highest risk is seen in CMV-seronegative recipients who receive a kidney from a CMV-seropositive donor. These patients are usually given antiviral prophylaxis.
Renal transplant infections
What is the usual time frame you would expect cytomegalovirus infection in renal transplant patients and why?
Cytomegalovirus tend to be seen after four weeks as before this time the immune system has not been fully affected by the immunosuppressants.
Upper zone vs Lower zone fibrosis
CHARTS
Acronym for causes of upper zone fibrosis:
CHARTS
C - Coal worker’s pneumoconiosis
H - Histiocytosis/ hypersensitivity pneumonitis
A - Ankylosing spondylitis
R - Radiation
T - Tuberculosis
S - Silicosis/sarcoidosis
Causes of lower zone lung fibrosis
idiopathic pulmonary fibrosis
most connective tissue disorders (except ankylosing spondylitis) e.g. SLE
drug-induced: amiodarone, bleomycin, methotrexate
asbestosis
What is the purpose of measuring ABPI and the normal value
a ‘normal’ ABPI may be regarded as between 0.9 - 1.2. Values below 0.9 indicate arterial disease.
ABPI
What indicates arterial calcification?
Interestingly, values above 1.3 may also indicate arterial disease, in the form of **false-negative **results secondary to arterial calcification (e.g. In diabetics)
Drug induced lupus
Features
* arthralgia
* myalgia
* skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common
Drug induced lupus - immunology
- ANA positive in 100%, dsDNA negative
- anti-histone antibodies are found in 80-90%
- anti-Ro, anti-Smith positive in around 5%
Drug induced lupus
Causes - and indicate the top two
Most common causes
* procainamide
* hydralazine
Less common causes
* isoniazid
* minocycline
* phenytoi
Lateral medullary syndrome
PICA
Presentation
* Ipsilateral CN palsy eg facial numbness
* Contralateral body loss of pain sensation
* Nystagmus, ataxia
Describe AICA and difference in presentation with PICA or lateral medullay syndrome
An anterior inferior cerebellar artery infarct would present in the same way but with the additional symptoms of a same-sided facial weakness and loss of hearing.
Subacute combined degeneration of the spinal cord
dorsal column involvement
* distal tingling/burning/sensory loss is symmetrical and tends to affect the legs more than the arms
* impaired proprioception and vibration sense
lateral corticospinal tract involvement
* muscle weakness, hyperreflexia, and spasticity
* upper motor neuron signs typically develop in the legs first
* brisk knee reflexes
* absent ankle jerks
* extensor plantars
spinocerebellar tract involvement
* sensory ataxia → gait abnormalities
* positive Romberg’s sign
