Inflammation Flashcards
What is viral load in HIV?
Number of viral RNA genomes /ml blood
Determined by RT-PCR - reverse transcription-linked polymerase chain reaction
How can you diagnose HIV?
Presence anti-p24 (Capsid) antibodies via ELISA
Only detects individual seroconverted, 3 months after infection
Positive samples re tested mit diff ELISA/Western Blot
What test can detect HIV before the individual has seroconverted?
RT-PCR
What is the common treatment for HIV?
Highly Active Anti-Retroviral Therapy (HAART)
2 x Nucleoside Reverse Transcriptase Inhibitor (NRTI)
PLUS
1 x Non Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
OR
1 x Protease Inhibitor
What joints are affected first in osteoarthritis?
Weight-bearing joints e.g. knees and hips
What defines a retrovirus?
Reverse transcription, copying RNA template (viral genome) ==> double-stranded DNA copy
Integration: covalent insertion of viral cDNA into genome of infected cell, forms provirus
What 3 types of polyproteins do retroviruses synthesise?
Gag: group specific antigen
Pol: polymerase
Env: envelope glycoprotein
What are some examples of the polyproteins retroviruses synthesise?
Gag: viral core proteins, MA (matrix), CA (capsid), NC (nucleocapsid)
Pol: PR (protease), RT (reverse transcriptase), IN (integrase)
Env: SU (surface), TM (transmembrane)
What are the 2 ways a retrovirus can enter a cell?
Receptor mediated endocytosis
Direct fusion of lipid bilayers (e.g. HIV)
How long does retrovirus life cycle take under permissive conditions?
24 hours
What is the negative effect of HIV reverse transcriptase having no proofreading activity?
Contributes to immune escape + drug resistance
What are some example of drugs to treat HIV that are entry inhibitors?
CCR5 inhibitor
Fusion inhibitor
What are the 2 classes of reverse transcriptase inhibitors for treatment of HIV?
Nucleoside-analogue reverse transcriptase inhibitors (NRTI) - incorporate ==> elongating DNA chain, X 3’OH leads to chain termination
Non-nucleotide Reverse transcriptase inhibitors (NNRTI). Allosteric RT inhibitors, X bind active site
Block initiation of RT
What drug affects integrase in the treatment of HIV?
Raltegravir, binds active site of Integrase, blocks strand transfer reaction
How do protease inhibitors work to treat HIV?
Inhibit HIV protease specifically, prevent cleavage of Gag + Gag-Pol to mature proteins
New virus particle non-infectious
What genetic predispositions can an individual have to get rheumatoid arthritis?
Human Leukocyte Antigen - HLA-DR1 + HLA-DR4
What is citrullination? How is it a part of rheumatoid arthritis?
Type II collagen + Vimentin modified
Arginine ==> Citrulline
Susceptibility genes (HLAs) mean immune system no longer recognises proteins as self and attacks
What is Charcot’s triad? What condition does it represent?
Jaundice, pain in URQ, rigors
Ascending cholangitis
What is Courvoisier’s law in regards to jaundice?
In presence of jaundice, if gall bladder palpable and non tender, jaundice unlikely due to stones
consider malignancy - pancreatic/gallbladder cancer
What illnesses are common in these countries?
a) Africa
b) Asia
c) SE Asia
a) Malaria
b) Typhoid
c) Dengue virus
What are key parts of the patients travel history should you keep in mind?
When travelled - incubation periods (time from exposure to symptoms)
What they did - business/posh hotels less risk compared to backpacking
What are the features of severe falciparum malaria?
confusion/fits acute renal failure respiratory failure hypoglycaemia acidosis hyperparasitaemia
What would you use to treat falciparum malaria?
IV artesunate (or quinine if artesunate x available)
How would you treat viral pharyngitis?
Symptomatic management e.g. analgesia
How would you treat pneumocystis jirovecii (PCP)?
Co-trimoxazole
Corticosteroids (prednisolone)
Oxygen therapy
Definition of healthcare associated infection?
Occurring cos of healthcare activity, not incubating at time of initial healthcare exposure
Cut off usually 48-72 hours
What different shapes can bacteria be identified by?
Coccus - round
Bacillus - rod shaped
Coccobacilli - oval shaped
What colour are these types of bacteria when stained?
a) Gram +ve
b) Gram -ve
a) Purple-blue
b) Red
What type of toxins do these bacteria produce?
a) Gram +ve
b) Gram -ve
a) Exotoxins, have teichoic acid in cell wall
b) Endotoxins in cell wall
What type of bacteria survives well on drying?
Gram +ve
What type of bacteria produces spores?
Gram +ve - some of them, not all
What are the class one antibiotics? What are the class 2 antibiotics?
Beta lactams, Aminoglycosides, Macrolides
Tetracyclines, Fluoroquinolones, Glycopeptides
What is the common gram positive cocci in clusters?
Staphylococcus aureus
What organism is the most common cause of septic arthritis?
Staphylococcus aureus
What is the common gram positive cocci in pairs and chains?
Streptococci
What are the two common gram -ve cocci?
Neisseria meningitidis
Neisseria gonorrhoeae
What is the eclipse phase in viral infections?
Period from virus entry until new infectious virons released
Definition of prodrome in viral infections
Non-specific symptoms appearing before more specific features (usually rash)
Definition of Reproductive Number (R0) in viral infections
Average no of secondary cases arising from a single index case in a totally susceptible population
When would you use an oral glucose tolerance test?
During pregnancy for gestational diabetes
Diabetes hasn’t been around long enough to affect Hb1aC
What are some microvascular complications of diabetes?
Retinopathy
Nephropathy
Neuropathy
What are some macrovascular complications of diabetes?
Cerebro-vascular disease
Ischaemic heart disease
Peripheral Vascular
Diabetic foot
What type of diabetes is ketosis prone?
Type 1
How is diabetes diagnosed?
Symptoms of hyperglycaemia
↑ blood glc conc/HbA1c
Venous plasma glucose ≥ 11.1 mmol/l
HbA1c ≥ 48 mmol/mol
How is diabetes diagnosed in asymptomatic patients?
On 2 separate occasions any of:
HbA1c ≥ 48 mmol/mol (≥6.5%)
Fasting venous plasma glucose ≥7 mmol/l
Random or 2h post 75 g glucose load ≥11.1 mmol/l
How is prediabetes diagnosed?
HbA1c 43 – 47 mmol/mol (6.1-6.4%)
fasting venous plasma glc - 6.1 - 6.9 mmol/l
Why would you not use a glucometer (capillary) to diagnose diabetes?
Venous plasma more accurate
Need to make sure of diagnosis
What ketones produced lead to metabolic acidosis on DKA?
acetoacetate
3 hydroxy-butyrate
Organic acids
Why are potassium levels affected in DKA?
Insulin causes K+ to move into cells
Without it, high extracellular K+, hyperkalaemia
Renal K+ loss, whole body K+ depletion
What antibody complexes are formed in RA?
IgG and IgM
Difference between osteoclast and osteoblast?
Osteoclast - breakdown of bone
Osteoblast - formation of bone
What do the pro-inflammatory mediators in RA do?
Promote tissue remodelling + damage
Stimulate macrophages, fibroblasts, osteoclasts, neutrophils
What genetic predisposition can make you more susceptible to develop RA?
HLA-DR1
HLA-DR4
QKRAA
What would you see on imaging in osteoarthritis (mnemonic)?
L - loss of joint space
O - osteophytes
S - subchondral sclerosis
S - subchondral cysts
What would you see on imaging in RA (mnemonic)?
L - loss of joint space
E - erosions
S - soft bone (osteopenia)
S - soft tissue swelling
What condition does smoking actually reduce the risk of?
Ulcerative colitis
What are the different classifications of ulcerative colitis depending on what parts of the colon are affected?
Proctitis - only rectum
Left-sided colitis - rectum + descending colon
Pancolitis - all of colon
What antigens are the primary target of the immune system on a transplanted organ?
HLA antigens
What type of organ donors are there?
Donation after brain death
Donation after circulatory death
Living donor
Expanded Criteria (EC) donor
When can anti-HLA antibodies develop?
After exposure to blood products, pregnancies, prior transplants
Where are the different classes of HLA antigens presented?
Class I - all nucleated cells
Class II - on APC (B cell, monocytes, dendritic cells), activated endothelial cells
What are the 3 types of HLA antibodies?
A, B, DR
When may a patient have pre-formed anti-HLA antibodies?
Pregnancy, Blood transfusions, Previous transplant
What 4 key principles aid in donor-recipient matching in kidney transplantations?
ABO compatibility
Best HLA match (DR>B>A)
No pre-formed anti-donor HLA antibodies
Minimise cold ischaemia time
When may A2 kidney donors be transplanted into O or B recipients?
If anti-A antibody titres are low (<1:8)
What test result is an absolute contraindication for renal transplantation?
Positive CDC T-cell crossmatch
When is risk of acute rejection and graft loss highest during kidney transplantation?
1st 3 months
How do NSAIDs increase the risk of peptic ulcers?
Inhibit COX-1, reducing prostaglandin production - cytoprotective
How does the Helicobacter pylori bacteria cause peptic ulcers?
Burrow into mucosa, allowing acid to reach other layers
Why may amylase levels be normal if taken 24-48 hours later in a patient with pancreatitis?
Excreted by kidneys
What obstructions can cause appendicitis?
Inflamm of vermiform appendix Faecolith Stool Infective agents Lymphoid hyperplasia
What is the common bacteria in appendicitis?
Bacteroides fragilis + E coli
What type of T helper response is prominent in:
a) U.C?
b) Crohn’s?
a) Th2
b) Th1
What does a stool MC&S test in U.C and Crohn’s exclude?
Campylobacter, C.diff, Salmonella, Shigella, E.Coli, Amoeba
What are the 3 features of renal bone disease/CKD -MBD?
Osteomalacia - softening of bones
Osteoporosis - brittle bones
Osteosclerosis - hardening of bones
What is the most common cause of nephrotic syndrome in:
a) Children?
b) Adults?
a) Minimal Change disease
b) Focal Segmental glomerulosclerosis
What is the most common cause of primary glomerulonephritis?
IgA nephropathy AKA Berger’s disease
What is an:
a) Uncomplicated UTI?
b) Complicated UTI?
a) Female, first presentation, not pregnant, immunocompetent
b) male, recurrent UTIs, elderly, catheter related, children, pyelonephritis
What is pyuria?
Presence of WBC in urine, >10 per HPF x400
What part of the urinary tract is involved in:
a) Upper UTIs?
b) Lower UTIs?
a) Kidneys and ureters
b) Bladder, Urethra, Prostate (male)
What are some examples of:
a) Upper UTIs?
b) Lower UTIs?
a) Pyelonephritis, Intrarenal/perinephric abscess
b) Cystitis, Urethritis, Prostatitis
What bacteria is the most common cause of UTIs?
Acronym for most common ones?
E. Coli
SEEEK PP - Saprophyticus, E.Coli, Enterococcus. Enterobacter, Klebsiella, Proteus, Pseudomonas
What is an ascending infection in UTIs?
Bact move from rectal area → urethra → bladder → kidney
What is a descending infection in UTIs?
Bact starts in blood/lymph → kidney → bladder → urethra
Why is antibiotic Nitrofurantoin avoided in 3rd trimester of pregnancy in treatment of UTIs?
Linked with haemolytic anemia in new-born
What arteries and veins are used to make a arteriovenous fistula?
Radiocephalic, Brachiocephalic, Brachiobasilic
What enzyme converts unconjugated bilirubin to conjugated bilirubin?
Glucuronyl transferase enzyme
Definition of:
a) Jaundice
b) Icterus
a) yellow discoloration of skin, mucous membranes and sclera due to hyperbilirubinemia
b) specific yellow discolouration of sclera due to hyperbilirubinemia, usu visible before jaundice develops elsewhere
Why would you get gynaecomastia in alcoholic liver disease?
Liver breaks down oestrogen, so when it’s ill, cannot break down
What is the difference between compensated and decompensated liver cirrhosis?
Compensated - liver is coping, no symptoms
Decompensated - liver x cope, symptoms
What can be given to help patients with diabetes insipidous?
Desmopressin - synthetic ADH
What 2 things increase calcium levels in body?
PTH Vit D (Calcitonin)
What is the role of PTH?
Increase:
osteoclast activity in bones (reabsorbing Ca from bones)
Ca absorption from the gut
Ca absorption from the kidneys (LoH + distal tubules)
Vit D activity - turn to active form
What is primary hyperparathyroidism?
How treat?
Tumor (adenoma commonly) in parathyroid gland
Hypercalcaemia, low phosphate,
Surgically remove tumour
What is secondary hyperparathyroidism?
How treat?
Low Vit D intake/chronic renal failure, low Ca resorbed (hypocalcaemia) so high levels PTH
Correct Vit D insufficiency/renal transplant
What is tertiary hyperparathyroidism?
How treat?
After prolonged secondary hyperparathyroidism, hyperplasia of glands
When secondary treated. PTH still high so hypercalcaemia
Surgically remove PT gland so PTH normal
What is primary hypoparathyroidism?
How treat?
decreased PTH gland failure/parathyroid surgery
low Ca, high phosphate
Ca supplement (alfacalcidol)