LO Related (Part 3) Flashcards
What is ECOLOGICAL FALLACY
Error that arises when information about groups of people is used to make inferences about individuals
Causes of a raised anion gap metabolic acidosis
Severe kidney dysfunction
Ketoacidosis
Ingestion of acid
Lactic acidosis
Describe the two theories that allow AUTOREGULATION of GFR
MYOGENIC - contraction and relaxation of the afferent arteriole that results from the the ammount of strech caused by systemic BP
TUBULOGLOMERULAR - Macula densa cells in contact with the JGA monitor Na content can can relase vasoactive mediators
What drugs can IMPAIR RENAL FUNCTION
NSAIDS
ACEi/ARBS
Cyclosporin
Aminoglycoside antibitiotcis (e.g. gentamycine)
What is BIAS
Systematic DEVATION from the TRUTH
What is a CONFOUDNING VARIABLE
A factor other than the independent variable that may produce detectable results
FOUR phases of a CLINICAL TRIAL
Phase 1 - safety - small numbers of health patients
Phase 2 - large numbers of disease individuals
Phase 3 - full scale evaluation compared to the standard treatment
Phase 4 - post marketing surveillance
What is the creatinine clearance rate
What is it useful for?
Volume of blood plasma that is cleared of creatinine per unit time
This is a useful measure for approximating GFR
Creatinie clearance provides OVER/UNDER estimate of GFR
Over
There is some Cr secretion into the filtrate
Causes of pre-renal AKI
Hypovolaemia
Decreased renal perfusion
Causes of intra-renal AKI
Direct damage to the kidneys via inflammation, drugs and infections
Cloudy and lumpy urine can be a sign of
UTI
Acute complications of AKI
Fluid retention
Hypercalaemia
Increased urea and creatinine
Metabolic acidosis
Criteria for RRT (renal replacement therapy)
Worsening hyperkalaemia
Worsening acidosis
Fluid overload
Symptomatic uraemia
Strenghts and weaknesses of a CROSS SECTIONAL STUDY
+ fast, inexpensive, no loss to follow up, good for looking at prevalence
- cant est causation, difficult with rare diseases
Strengths and weaknesses of a CASE CONTROL study
+ fast, inexpensive, good for rare disease
- recall bias
Stengths and weaknesses of a COHORT study
+ assess multiple outcomes/exposures, demonstrate causality
- time consuming, expensive, not good for rare diseases
What is the role of the 3 consitiutent parts of the FILTRATION BARRIER
CAP ENDOTHELIUM - stops blood cells
BASEMENT MEMBRANE - stop large proteins moving across, also repels -ve molecules
PODOCYTES - allow small ions through but not PROTEINS
Define AKI
Failure of renal function over hour days characteristed by a rise in serum urea and creatinine
Reversible
What is the creatinine clearance rate
What is it useful for?
Volume of blood plasma that is cleared of creatinine per unit time
This is a useful measure for approximating GFR
Creatinie clearance provides OVER/UNDER estimate of GFR
Over
There is some Cr secretion into the filtrate
Causes of pre-renal AKI
Hypovolaemia
Decreased renal perfusion
Causes of intra-renal AKI
Direct damage to the kidneys via inflammation, drugs and infections
Cloudy and lumpy urine can be a sign of
UTI
Acute complications of AKI
Fluid retention
Hypercalaemia
Increased urea and creatinine
Metabolic acidosis
Criteria for RRT (renal replacement therapy)
Worsening hyperkalaemia
Worsening acidosis
Fluid overload
Symptomatic uraemia
Nephrotic diseases
Main symptoms
How do they come about
Generally due to DAMAGE to the BASEMENT MEMBRANE or to the PODOCYTES
Proteinuria
Strengths and weaknesses of a CASE CONTROL study
+ fast, inexpensive, good for rare disease
- recall bias
Stengths and weaknesses of a COHORT study
+ assess multiple outcomes/exposures, demonstrate causality
- time consuming, expensive, not good for rare diseases
What is the role of the 3 consitiutent parts of the FILTRATION BARRIER
CAP ENDOTHELIUM - stops blood cells
BASEMENT MEMBRANE - stop large proteins moving across, also repels -ve molecules
PODOCYTES - allow small ions through but not PROTEINS
Define AKI
Failure of renal function over hour days characteristed by a rise in serum urea and creatinine
Reversible
How can NSAIDS lead to AKI
NSAIDS inhibition production of PROSTAGLANDINS
Local prostaglandins relax the afferent arteriole
So NSAIDS lead to constriction of the afferent arteriole and decreased perfusion
Most common (3) causes of CKD
Diabetes
Hypertension
Glomerulonephrtisi
3 major functions of the kidney in ACID BASE BALANCE
1) Reabsorption of filtered bicarbonate
2) Excretes excess acid - as phosphoric acid and ammonium
3) Forms new bicarbonate through breakdwon of carbonic acid and glutamine
What is Anti-GBM disease?
What it also caused
ANTI-GBM = GOODPASTURES
Pulmonary and renal disease caused by anti-GBM antibodies
Anti-GBM nephrotic or nephritic
Nephritic
Give an example (and the MOA) of an antibody that promotes immune system activation
ANTI-CLTLA-4 (ipilimumab)
Minimal change disease is an example of which kind of disease
Nephrotic
What is the inner layer of the spleen
What is its function
White pulp
WBC action (removal of antibody coated microbes) and synthesis of antibodies
Reservoir of monocytes
MOA Corticosteroids
Lipid soluble
Binds steroid receptor - DIMERISATION
Steroid receptor complex activates/inhibits pro/anti inflammatory genes in the nucleus
Describe how INDIRECT ALLORECOGNITION is able to occur
Peptides from donor MHC and minor HLA antigens presented to recipient T cells on MHCII on APCs
Activation of recipitent T cells
Production of chornic inflammaotry cycle
Non-immune causes of glomerular disease
Diabetes
Amyloidosis
What occurs in IgA nephropathy
Is Iga nephropathy nephrotic or nephritic
IgA depsition in the mesangium - the most common form of primary glomeruluonephrtisi
This is a NEPHRITIC disease
Describe how DIRECT ALLORECOGNITION occurs
Intact foreign MHC presented directly to T cells
Recipient T cells activated
Recipient T cells attack foreign tissue
Main HLA loci to avoid mismatches
A B DR
What is SLE
What sort of disease does it cause?
Systemic lupus erythematosus
Causes immune mediated glomerular disease
What happens in MEMBRANOUS NEPHROPATHY
Subepithelial immune deposits often due to autoantibodies
Chancges in the basement membrane
What is the worst HLA mismatch that you can have
HLA-B7-positive to HLA-A1-positive
Minimal change disease is an example of which kind of disease
Nephrotic
How does diabetes cause CKD
Hyperglycaemia causes non enzymatic glycation of the efferent arteriole - this makes it STIFF AND NARROW
Leads to an increased pressure in the kidney leading to hyper-filtration and glomerulosclerosis
Describe why CORTICOSTEROIDS are good for PREVENTING transplant REJECTION
- Decrease cellular response to pro-inflammatory cytokines
- Suppressed chemotactic and inflammatory mediators
- Reduced activation and expression of MHCII on macrophages
- Reduced recruitment of white blood cells
Symptoms of NEPHRTIC SYNDROME
What is usually the underlying cause
Give one example
Haematuria with hyperalbuminaemia and hyperlipidaemia
Usually due to GLOMERULAR INFLAMMATION
E.g. IgA nephropathy
Pros of HAEMODIALYSIS
Predictable
Can be monitored by healthcare professional
Only 3/4 times per week
What are the potential issues associated with the use of CORTICOSTEROIDS
Suppress pre-existing innate and adaptive immunity
Long term can lead to Cushings syndrome
Also long team - patients need to be WEANED off since the steroids will suppress production of corticotrophin releasing hormone by the hypothalamus
ANP inhibits what channel
What does this promote
ENaC
Naturesis
How can amyloidosis lead to CKD
What type of syndrome does it cause
Abnormal deposition of amyloid proteins
Leads to a NEPHRITIC disease
Define (in words) specificity
The proportion of people without the disease who test negative
What happens in MEMBRANOUS NEPHROPATHY
Subepithelial immune deposits often due to autoantibodies
Chancges in the basement membrane
Symptoms of acute pyelonephrtisi
Fever
Loin pain
Tenderness
What does NEGATIVE LIKELIHOOD RATIO show
Give the formula
How much more likely a negative test is in a person without the disease than in a person with the disease
(1 - Sensitivity) / Specificity
What is KOILONYCHIA
What is it a sign of
Spooning of the nails
Seen in iron deficient anaemia
In what form is iron most easily absorbed
Fe2+ or as haem
Example of an INTRAVASCULAR RBC defect that causes HAEMOLYSIS
Transfusion reaction
Infection
Prosthetic heart valves
Snake/spider bites
Example of an INTRINSIC RBC DEFECT that causes HAMEOLYSIS
Enzyme deficiency or membrane defect
What does a likelihood ratio of LESS THAN 1 mean
Test result is associated with absnecne of disease
Further from 1 = stronger associaion
Causes of microcytic anaemia
Iron deficient anaemia
Hamoglobinopathies - thalassaemia
Sideroblastic anaemia
Lead poisoning
Define (in words) specificity
The prop
Coombs test is a trst for
HAEMOLYTIC ANAEMIA
Give some examples of drugs that can cause anaemia
NSAIDS Metformin High dose penicillins Ranitidine Furosemide Warfarin Glitazones
Causes of a NORMOCYTIC anaemia
Anaemia of chronic disease
Acute blood loss
Mixed deficiency
Bone marrow failure
Bruising under the skin is a sign of which anaemia
Haemolytic
What is myelodysplasia
Family of bone marrow failure syndromes
Example of an EXTRINSCI RBC defect that causes HAMEOLYSIS
Autoimmune haemolytic anaemia
Liver disease
Infections
Drugs
Stimuli for the release of gastrin
What is the main effect of gastrin
Where is it released from?
Rising gastric pH
Neural (vagal) stimulation
Presence of partially digested food
INCREASES GASTRIC ACID SECRETION AND MOTILITY
Released from G cells
What does a likelihood ratio of greater than 1 mean
Test result is associated with presence of disease
The further from 1 it is the greater the association
Causes of microcytic anaemia
Iron deficient anaemia
Hamoglobinopathies - thalassaemia
Sideroblastic anaemia
Lead poisoning
Structure and classification of H. Pylori
Gram -ve
Helical
Flaggella
Transamination describes the conversion OF WHAT, TO WHAT
Amino acid –> Keto acid
What is CORNEAL ARCUS
Lipid deposition in the cornea
Sign of hypercholesterolaemia
Pancreas develops from a
DORSAL AND VENTRAL bud on the duodenum
What is proctitis
Inflammation of the rectum - this is commonly seen in ULCERATIVE COLLITIS
Symptoms of duodenal ulcers
Weight gain
Eating that reduces pain
What are BRUNNERS GLANDS
What do they produce
Glands that are unique to the duodenum
Secrete bicarbonate to neutralise stomach acid
Stimuli for the release of gastrin
What is the main effect of gastrin
Where is it released from?
Rising gastric pH
Neural (vagal) stimulation
Presence of partially digested food
INCREASES GASTRIC ACID SECRETION AND MOTILITY
Released from G cells
Everyone with coeliac has which MHCs
DQ2 and DQ8
What is APECED
Autoimmune condition arising from the last of expression of self antigens in the thymus
Structure and classification of H. Pylori
Gram -ve
Helical
Flaggella
Ways in which Tregs suppress activation of CD4
Contact dependent killing and suppression
High levels of CD25 (mop up IL-2)
Hi CTLA-4 (mops up CD80/86)
Bystander effect on nearby cytokines
Production of immunosuppressive cytokines - IL-10
Defect in FOXP3 leads to
IPEX
