Clinical Sciences Flashcards
On which chromosomes are the genes which encode for HLA proteins?
6
What is the difference between MHC Class I and Class II?
Class 1 = Surface of all cells, Allow for Cytotoxic/NK T cells to rcognisde viral/tumour antigens produced within the cell, CD8
Class 2 = Surface of APCs, involved in antigen presenting of extracellular pathogens, CD4
Which diseases are most associated with HLA B27?
AS
Post-gonococcal Arthritis
Acute Anterior Uveitis
Reactive Arthritis
Which disease are most associated with HLA DR2?
Narcolepsy
Goodpasture’s
Which diseases are most associated with HLA DR3?
Autoimmune hepatitis
PBC
T1DM
Dermatitis Herpetiformis
Coeliac
Sjogren’s
Which diseases are most associated with HLA DR 4?
RA
T1DM
Which disease is most associated with HLA DR3 and 4 together?
T1DM
Which disease is most associated with HLA B47?
21-hydroxylase deficiency
Which diseases are most associated with HLA A3?
Haemochromatosis
Which HLA is associated with Behcet’s?
HLA-B5
What is Felty’s Syndrome?
Triad of:
RA
Splenomegaly
Neutropaenia
Highly associated with HLA DR4
What are CD1 molecules?
HLA molecules with present lipid molecules
What are CD2 molecules?
Found on thymocytes, T cells and some NK cells
Act as a ligand for CD58 and CD59 - signal transduction and cell adhesion
What are CD3 molecules?
The signalling component of the T-Cell Receptor
What are CD4 molecules?
Co-receptor for MHC Class I
Which receptors are used by HIV units to enter T Cells?
CD4
What are CD8 molecules?
Co_receptor for HLA Class I
Also found on a subset of myeloid dendritic cells.
What are type I hypersensitivity reactions?
IgE mediated anaphylactic reaction provoked by re-exposure to an allergen. Allergies, Hayfever etc = type 1
Which anaphylactoid reactions aren’t IgE mediated?
NSAIDs, IV Contrast, Opioids, Exercise-allergy
How do NSAIDs cause anaphylactoid reactions if not IgE mediated?
COX-1 inhibition -> Reduced prostanglandins, more leukotrienes = bronchoconstriciton, urticaria and pruritus
What are Type II hypersensitivity reactions?
IgG/IgM Mediated
Antibody reacts with cell/matrix associated self-antigen.
Leads to tissue damage/receptor blockade/receptor activation
Which test would be positive in autoimmune haemolytic anaemias and which HS type are they?
Direct Coombs
Type II
What are type III hypersensitivity reactions?
IgG/IgM immune complex mediated (Ab vs Soluble Ag)
List 4 disease caused by Type III HS reactions
Mixed essential Cryoglobulinaemia
Serum Sickness
Polyarteritis Nodosa
SLE
What are Type IV hypersensitivity reactions?
T-Cell mediated
Delayed
List 4 diseases caused by Type IV hypersensitivity reactions
T1DM
MS
RA
Crohn’s
What is Type V hypersensitivity?
IgG mediated tissue damage
Graves’, MG
What are skin prick tests used for?
Food Allergies
Pollen
Insect venom (bee stings etc.)
Take 15 mins
Histamine pos. control & H2O neg. control used alongside ?allergen
What is RAST?
Radioallergosorbent testins
Grades level of IgE response to allergens
Food, Pollen, Insect venom
Graded 0 (negative) to 6 (strongly positive).
What is skin patch testing used for?
Contact dermatitis
What are monocytes
APCs produced in BM
Migrate via blood to tissues where they differentiate to macrophages
What roles do IgG antibodies have?
Activate Classical complement pathway
Bind to macrophages & neutrophils for enhanced phagocytosis
Bind to NK Cells for antibody-dependent cytotoxicity
Which antibodies can cross the placenta?
IgG
What roles do IgA antibodies have?
Blocks attachment of bacteria/viruses to mucous membranes preventing internalisation
Exist in bodily secretions
Activates Alternative complement pathway
What roles do IgM antibodies have?
First antibody produced in acute immune response
Can activate classical complement pathway
Some exist on surface of B cells as BCRs
What roles do IgD antibodies have?
Found on surface of B-Cells as B-Cell receptors
Prevent B-cells from generating autoantibodies
What roles do IgE antibodies have?
Bound to Basophils/Mast cells
Parasitic reactions (Opsonise eosinophils vs parasites/arthropods)
Promote inflammation in external mucous membranes
What is deficient in Chronic Granulomatous Disease, Chediak-Higashi Syndrome and Leukocyte adhesion deficiency?
Neutrophils
What is deficient in IgA Def., bruton’s congenital Agammaglobulinaemia and Common variable immunodeficiency?
B-Cells
What is deficient in DiGeorge’s and which infections are patients most susceptible to?
T-Cells
Viral & Fungal
Which immunodeficiency disorders are of mixed T/B cell pathophysiology?
Severe Combined
Ataxic telangiectasia
Wiskott-Aldrich Syndrome
Describe the inheritance and presentation of Wiskott-Aldrich Syndrome
X-Linked recessive
WASP gene mutation
Recurrent bacterial infections, eczema and thrombocytopenia with low plasma IgE
What are ANCA?
Anti-neutrophil cytoplasmic antibodies.
P=Perinuclear
C=Cytoplasmic
Which 2 diseases are most strongly associated with cANCA and what is the most common chemical target?
Wegener’s Granulomatosis
Microscopic Polyangiitis
Serine Proteinase 3
cANCA levels = marker of disease activity
Which diseases are most commonly associated with pANCA and what is the most common chemical target?
Immune Crescentic Glomerulonephritis
Microscopic Polyangiitis
Churg-Strauss
Wegener’s (weakly vs cANCA)
Myeloperoxidase
What is complement?
A group of 20 tightly regulated, linked proteins produced in the liver and present as inactive molecules in the circulation.
When triggered, enzymatically activate other proteins in a biological cascade resulting in a rapid, highly amplified immune response resulting in the formation of a ‘membrane attack complex’ which punctures holes in bacterial cell membranes.
Which protein is, when activated, the catalyst for the major amplification step of the complement cascade?
C3
What is C1 inhibitor protein deficiency?
Complement deficiency resulting in Hereditary Angioedema.
Uncontrolled bradykinin release leads to tissue oedema.
Which components are present in the classical complement pathway?
C1q
C1rs
C2
C4
Which diseases are caused by deficiency of the components of the classical pathway of complement?
Immune complex disease ie. SLE, Henoch-Schonlein purpura
(C2 most common - almost all C2 deficient pts have SLE)
What happens with C3 deficiency?
Recurrent Bacterial infections
Especially encapsulated bacteria (Mening. Haemoph., Streptoc.)
Which disease is caused by C5 deficiency?
Leiner Disease
A long-term seborrheic dermatitis associated with increased susceptibility to infection (incl. disseminated meningococcal), diarrhoea and wasting.
What occurs with C5-C9 Deficiency (Terminal common pathway)?
Cannot form MAC
Prone to:
Neisseria meningitides
Haemophilus influenza
Steptococcus pneumoniae
How is anion gap calculated?
(Na+K)-(Cl+HCO3-)
Pos - Neg
Normal = 10-18
What are the main causes of a normal anion gap metabolic acidosis?
GI Bicarb Loss
RTA
Drugs (Acetazolamide = common)
Ammonium Chloride injection (used in sev. met. alkalosis)
Addison’s
What are the main causes of a raised anion gap metabolic acidosis?
Lactic acidosis
Ketoacidosis
Uric (renal failure)
Acid Poisoning (salicylates, methanol)
What may cause a metabolic alkalosis?
Vomiting/Aspiration
Diuretics
Hypokalaemia
Prim. Hyperaldosteronism
Con. Adrenal hyperplasia
Cushing’s
Bartter’s
What is the difference between osmolality and omsolarity
Osmolality = Total particles/kg (measured with osmometer in mmol/kg)
Osmolarity = total particles /L (calculated 2(Na+K)+Urea+Glucose)
Why is knowing both osmolarity and osmolality useful?
Osmolality and Osmolarity should roughly equate, with osmolality being an exact measured figure.
Physiological solutes should just be Na, K, Cl, HCO3, Urea and Glucose.
If there is a difference (raised osmolar gap) then we can assume there are pathological solutes in the blood, such as glucose, ethanol or mannitol.
How are true vs pseudo hyponatraemia differentiated?
Serum Osmolality
Would be low if true
Lab machines measure Na/Volume and assume it is Na/Water
If Osmolarity = normal/high there is increased volume due to protein/lipid/extra solutes. As such total volume is bigger but Na remains the same, hence is reported by the lab as having been diluted.
What is TURP syndrome?
Glycine 1.5% is used to irrigate the prostate during resection.
If this is absorbed and metabolised, leads to hyponatraemia
What is the first step in assessing a true hyponatraemia?
Assess volume status
How would you assess and treat a hypervolaemic hyponatraemia?
Check urinary Sodium
If >20 = ?Renal = AKI/CKD
If <20 = ?Non-Renal = Cardiac Failure/Cirrhosis/Too much IVI
Fluid Restrict +/- Diuresis
Specialist input
How quickly can hyponatraemia be corrected and what is the risk?
8-10mMol/24h
Theoretical risk of central pontine myelinolysis (pseudobulbar palsy - evidence is limited)
How is euvolaemic hyponatraemia assessed?
Check:
TFTs
Short Synacthen
Paired urine/serum osmolality
Can be hypothyroid, addison’s
If not + high uNa + High urine osmolality + low plasma osmolality = ?SIADH
What can cause SIADH?
Malignancy - Small cell lung most common, pancreatic, prostatic, lymphoma
CNS pathologies
TB, Pneumonia, Chest abscess
Drugs
Which drugs can cause SIADH?
Opiates
SSRIs
TCAs
Carbamazepine
PPIs
How do you treat SIADH?
Fluid restrict + Treat the cause
How would you assess hypovolaemic hyponatraemia?
Urinary Sodium
If low - D/V, Ascites/Burns (£rd spacing) - Kidney is working
if high - Diuretics, Addison’s, Salt-losing nephropathies
How does Cirrhosis cause hyponatraemia?
Poor breakdown of vasodilators (eg. NO)
= Low BP
= More ADH
= Water retention = Dilution
How does Cardiac Failure cause hyponatraemia?
Low CO = ADH release
= Water retention = Dilution
BNP also natriuretic which worsens this effect
What are the main causes of hypernatraemia?
Hypovolaemic =
Low uNa = GI/Skin Losses
High uNA = Loop Diuretics, osmotic Diuresis (HHS), DI, Renal
Euvolaemic = DI, Skin/Breathing losses
Hypervolaemia = Conn’s, IVI
How are central/nephrogenic diabetes insipidus treated?
Central = Desmopressin
Nephrogenic = Thiazide Diuretics (paradoxical)
Which drugs most commonly cause hyperkalaemia?
K-Sparing Diuretics (Spironolactone)
ACEi
Cyclosporin
What are the main causes of hyperkalaemia?
AKI
Drugs
Metabolic Acidosis
Addison’s
Rhabdomyolysis
Massive Transfusion
What may cause hypokalaemia with alkalosis?
Vomiting
Diuretics
Cushing’s
Conn’s
What may cause hypokalaemia with acidosis?
Diarrhoea
RTA
Acetazolamide
Partially Treated DKA
What is Type 1 RTA?
Distal failure of H+ excretion = acidosis & hypokalaemia
Failure of hydrogen-K pump
What is type 2 RTA?
Proximal bicarb resorption failure -> acidosis -> hypokalaemia
What is type 4 RTA?
Aldosterone deficiency/resistance = acidosis and hyperkalaemia
What are the main causes of hypomagnasaemia?
Diuretics
TPN
Diarrhoea
Alcohol
Hypokalaemia
Hypocalcaemia
What are the main causes of hypophosphataemia?
Alcohol Excess
Liver Failure
DKA
Refeeding
Prim. Hyperparathyroidism
Osteomalacia
Where is calcitonin secreted and what does it do?
C Cells (parafollicular) in thyroid
On osteoclasts: Causes contraction = limited ability to resorb bone = low Ca (short term effect)
On tubules: Increased diuresis/reduced resorption = low Ca/Po4
What does PTH do?
Increases:
Renal tubular reabsorption of calcium
Osteoclastic activity
Renal hydroxylation of 25-hydroxy-vit d to 1,25-dihydroxy-vit d
Reduces renal phosphate resorption
What does vitamin D do
Increased renal tubular resorption or Ca and Po4
Increases gut absorption of Ca
Increases osteoclast activity
