Nephrology Flashcards
Differential diagnosis of Haematuria?
A genetic susceptibility and an exaggerated immune response to an URTI is the cause of a primary IgA nephropathy, but what are the causes of a secondary IgA nephropathy.
Differential diagnosis for micro/macro scopic Haematuria in an otherwise asymptomatic patient who has had Urological malignancy ruled out?
Genetic disorders
Thin membrane disease (relatively benign - painless haematuria)
Alports disease (Rare genetically inherited disorder that causes hearing loss, eye problems and an abnormal Glomerular Basement Membrane) - can cause renal failure - most patients end up on dialysis.
How do you diagnose IgA nephropathy?
Kidney biopsy
Only indicated if:
- Haematuria and proteinuria
- Haematuria w/ decling kidney fnc
Kidney biopsy goes through 3 phases, what are they?
- Light Microscopy (first image shows classic crescent shape of IgA nephropathy)
- Immunofluorescence (IHC)
- Transmission electron microscopy (TEM)
Which scoring system can be used to classify prognosis in IgA nepropathy
Oxford Classification (basically characterizes the the mesangium)
MEST-C
Mesangial hypercellularity
Endothelial Hypercellularity
Segmental Glomeruloscelrosis
Tubular atrophy / Interstitial Fibrosis
Crescent formation
The hallmark of treatment in IgA nephropathy is ____.
ACE-i
*Not steroids unless acute decline in renal function*
Most common cause of Glomerulonephritis?
IgA nephropathy
- especially prevalent in Caucasians and East Asians
- Men 2:1 Women
- Most common in 2nd and 3rd decade of life
*Remember can present with loin pain and thus may mimic renal calculi*
Pathophysiology of IgA nephropathy?
Genetic Susceptibilty - URTI - Exaggerated Immune Response - Antibody Complex form in Mesangium - Endothelial/Tubular damage
(i.e Endothelium/GBM/Podocyte interface is damaged)
Prognostic markers for glomerulonephritis other than the Oxford histology score (MEST-C)?
BP
Proteinuria (Remember proteinuria is significant in nephrology if >1g / 24hrs)
Renal function
Glomerular Disease:
Nephrotic vs Nephritic Syndrome
The key with nephrotic syndrome is an excess amount of protein in the urine, whereas nephritic syndrome is where there is an excess amount of blood in the urine.
Nephrotic Syndrome:
Injury to Podocytes (Proteinuria)
Changed mesangial architecture
(ex. Minimal change disease/ Diabetic nephropathy/ Amyloid)
Nephritic Syndrome:
Inflammation
Reactive cell proliferation
GBM disruption (slit membrane) - blood leaks into urine
Crescent formation
(Ex. Post-Streptococcal infection/Anti-GBM aka goodpasture’s disease - affects lung BM aswell/ANCA small vessel vasculitis)
As outlines above nephrotic syndrome is characterised by very heavy proteinuria (> 3.5 g/24 hrs), hypoalbuminaemia and oedema.
The Nephritic syndrome is characterised by the presence of haematuria frequently in association with hypertension, oliguria, fluid retention and usually (but not always) reduced / declining renal function. Patients with nephritic syndrome may also exhibit varying degrees of proteinuria, including nephrotic-range proteinuria; the prominence of haematuria on
dipstick should, however, alert the physician to the possibility of a glomerulonephritis.
Indeed, it is important to recognise that the characteristic features of nephritic syndrome and nephrotic syndrome do not always present in isolation, but should be considered to be the extreme phenotypes at either end of a spectrum of presentations.
Students should learn that damage to the podocytes causes (heavy)
proteinuria (see graph above) whilst the glomerular injury caused by Autoantibodies or Immune complex deposition usually causes haematuria +/- mild to moderate proteinuria.
At the other end of the spectrum, inflammation leads to cell damage and proliferation, breaks form in the glomerular basement membrane (GBM) and blood leaks into urine. In its extreme form, with acute sodium retention and hypertension, such disease is labelled nephritic syndrome.
The histology to the right shows a **glomerulus with many extra nuclei from proliferating intrinsic cells**, and influx of inflammatory cells leading to crescent formation (arrows) in response to severe post-infectious glomerulonephritis.
A blood test can be used to screen for post-infectious (usually streptococcus) glomerulonephritis, which circulating proteins are looked for?
Anti-streptolysin O titre (ASOT)
C3, C4 (complement proteins)
Draw out the RAAS system.
____ and ___ are the two most common causes of CKD.
Diabetic Nephropathy
Hypertensive Nephropathy
*Both lead to nephrosclerosis*
What are the 3 ways in which multiple myeloma causes renal disease?
Light chain cast nephropathy (intralubular collection of light chain-protein complexes) - most common
Light chain deposition disease (deposits in the glomerulus)
AL Amyloidosis
Hypercalcaemia and Hyperuricaemia (Tumour lysis syndrome causes tubular crystallization of uric acid) also possible causes of MM induced nephropathy.
Pathophysiology of Diabetic Nephropathy
Glycylated basement membrane and endothelial cells (due to hyperglycaemia) thicken and harden the efferent arteriole of the glomerulus.
This leads to increased pressure within the glomerulus and reduced reabsorption in the collecting tubules. The kidney thinks it needs a great blood supply and the afferent arteriole dilates but this only serves to increase pressure in the glomerulus and this is why the 1st/early stage of diabetic nephropathy actually leads to hyperfiltration.
The increased pressure and size of the glomerulus only serves to disrupt its architecture more and this leads to increased space between podocytes (slit junctions) leading to proteinuria and mesangial expansion. Mesangial expansion leads to increased ECM production - leading to collagenous nodules called Kimmelstiel - Wilson Nodules.
4 main events that contribute to diabetic nephropathy
- Thickened Glomerular Basement membrane
- Mesangial expansion
- Kimmelstiel - Wilson nodules
- Podoctye disruption
Remember ANCA vasculitis is a small vessel vasculitis caused by antibodies to the cytoplasmic contents of granulocytes (i.e neutrophils/basophils/eosinophil/monocytes).
This is why it is called granulomatosis with polyangiitis
Remember C-ANCA means _____
whereas pANCA means ____
Cytoplasmic - Anti-Neutrophil Cytoplasmic Autoantibodies
Perinuclear - Anti Neutrophil Cytoplasmic Autoantibodies
*note - Neutrophilic not Nuclear*
How do we classify an AKI?
KDIGO Classification (Stage 1, 2, and 3)
Measures from baseline Creatinine and Urine output in 12/24hrs
3 drugs to avoid in renal impairment (lecture)
Lithium -100% RC
Gentamicin (aminoglycaside) - 100% RC
LMWH (70% renal clearance)
(unfractionated LMWH can be used in renal dysfunction as it has a greater molecular weight and thus is not filtered by the kidney - essentially this means that it is less dependent on the kidneys for clearance and so we ar eless worried about the drug in patients with renal dysfunction)
When taken as an overdose, the metabolism of paracetamol results in a buildup of a toxic substance called _____.
NAPQI (N-acetyl-p-benzoquinone-imine).
NAPQI is inactivated by glutathione. In an overdose, glutathione stores are rapidly depleted, and NAPQI is left un-metabolised. It can cause liver and kidney damage.
Stages of Chronic Kidney Disease and active monitoring?
KDIGO (Kidney Disease Improving Global Outcomes)
Causes of Hyperkalaemia?
Reduced excretion from kidneys:
AKI
ACE inhibitors
Potassium Sparing Diuretics (ex spironolactone) but also diuretics in general
NSAIDs
Beta Blockers
K+ containing laxatives (movicol/fybogel)
Heparin (which inhibits aldosterone release)
Ciclosporin
Addison’s
Cellular Release:
Rhabdomyolysis
Digoxin Toxicity (NB - Can be precipitated by hypokalemaia) - “Reverse tick sign” on ECG
Tumour Lysis Syndrome
Massive Haemolysis
Acidosis:
DKA or any other metabolic acidosis
Hyperkalaemia is a potentially life threatening electrolyte abnormality.
Treat K+ >___ mmol/L or any hyperkalaemia with ECG changes with the following;
Give 10ml of 10% _____ (or chloride) over 10 mins - this is cardioprotective
Intravenous ____ (10u soluble insulin) in 25g ____ (50mL of 50% or 125ml of 20% glucose) - insulin causes intracellular K+ shift and glucose to required to prevent hypoglycaemia
Nebulised salbutamol - also causes intracellular K+ shift
Treatment with sodium bicarbonate is controversial
Other aspects of management:
Check contributing drugs (e.g. ACE inhibitors, spironolactone)
Once initial measures completed, recheck urea and electrolytes and ECG and glucose
Urinary potassium
Hyperkalaemia is a potentially life threatening electrolyte abnormality.
Treat K+ >6.5mmol/L or any with ECG changes with the following;
Give 10ml of 10% calcium gluconate (or chloride) over 10 mins - this is cardioprotective
Intravenous insulin (10u soluble insulin) in 25g glucose (50mL of 50% or 125ml of 20% glucose) - insulin causes intracellular K+ shift and glucose to required to prevent hypoglycaemia
Nebulised salbutamol - also causes intracellular K+ shift
Treatment with sodium bicarbonate is controversial
Other aspects of management:
Check contributing drugs (e.g. ACE inhibitors, spironolactone)
Once initial measures completed, recheck urea and electrolytes and ECG and glucose
Urinary potassium
Differential Diagnosis/ causes of SIADH
Malignancy - SCLC
Respiratory (LRTI - particularly legionella pneumonia / PE)
Neurological (SOL/CVA/ Trauma/SAH/Meningitis)
Drugs (Carbamazepine/SSRI’s/ PPI’s)
MNDR
Causes of Hyponatraemia?
Remember to classify into:
Hypovolaemic (In the elderly dehydration is a very common cause especially in patients with dementia)
Euvolaemic (SIADH / Hypothyroidism)
Hypervolaemic
and drugs:
Thiazide diuretics > Loop Diuretics > K+ sparing diuretics
Hyponatraemia Management
Criteria for diagnosing SIADH?
Low Serum Na (<135)
Low Serum Osmolality (i.e dilute plasma)
High Urine Osmolality (i.e concentrated urine)
High concentration of urine Na
Normal Renal/Cardiac/Thyroid/Adrenal function
No offending drugs
Euvolaemic fluid status
How do you calculate serum osmolality?
2 X Na + Glucose + Urea
Complications of Nephrotic Syndrome?
Infection (due to urinary loss of immunoglobulins) - sepsis if NS left untreated
Venous thromboembolism (due to urinary loss of antithrombin III)
Hyperlipidaemia (due to increased hepatic production of lipids to restore the serum oncotic pressure)
Nephrotic Syndrome is defined as the presence of ____ (>___g/____), ____
(<30 g/L), and _____ .
_____ and ____ disease are also
frequently seen.
NS defined as the presence of:
Proteinuria (>3.5 g/24 hours),
Hypoalbuminaemia (< 30 g/L)
Peripheral oedema
Hyperlipidaemia (liver tries to compensate for loss of albumin) and thrombotic disease (loss of clotting factors - antithrombin) are also
frequently seen.
Patients become hypoalbuminaemic due to the urinary loss of albumin. The liver tries to compensate for this protein loss by increasing the synthesis of albumin, as
well as other molecules including LDL and VLDL and lipoprotein(a), contributing to the development of lipid abnormalities including hypercholesterolaemia and
hypertriglyceridaemia (4).
Hypercoagulability results from the loss of inhibitors of coagulation in the urine and increased synthesis of procoagulatory factors by the liver (4). Hypercoagulable states predispose to venous thrombosis. Prolonged bed rest should be avoided, as
thromboembolism is very common.
Each kidney has approximately ____ glomeruli, which are the sites of blood filtration.
The layers of the glomeruli include the ____ of the
capillary, the _____ , and the _____ of the
podocytes.
The main barrier to filtration is the connection between adjacent _____ .
Viral infection, drugs, toxins or the local activation of the renin-
angiotensin system can cause direct injury to podocytes.
Electron microscopy in MCD (ex. Nephrotic syndrome) demonstrates diffuse effacement of the epithelial cell
foot processes and this disruption of the filtration barrier is understood to cause (heavy) glomerular proteinuria. However the Endothelium and GBM is untouched - hence the name MCD.
Each kidney has approximately 1 million glomeruli, which are the sites of blood filtration.
The layers of the glomeruli include the fenestrated endothelium of the capillary, the glomerular basement membrane, and the foot processes of the podocytes.
The main barrier to filtration is the connection between adjacent podocyte foot processes.
Viral infection, drugs, toxins or the local activation of the renin-
angiotensin system can cause direct injury to podocytes.
As outlined above the
electron microscopy in MCD demonstrates diffuse effacement of the epithelial cell
foot processes and this disruption of the filtration barrier is understood to cause
(heavy) glomerular proteinuria.
Causes of Nephrotic Syndrome:
The probable aetiology differs depending on the patient’s age
and the presence of specific comorbidities (e.g., diabetes, amyloidosis, or systemic
lupus erythematosus).
The most common cause in children is _____ .
In adults, primary glomerular diseases are more frequent in males
(55%), whereas secondary glomerular disease is more frequent in females (72%).
The most common cause in younger adults is _____ , followed by minimal change nephropathy.
______ is the most common cause in older people (8, 9) and diabetic nephropathy in adults with a
history of long-standing diabetes.
Nephrotic syndrome can also develop in patients with IgA nephropathy, membranoproliferative glomerulonephritis, and post-infectious glomerulonephritis.
However, these patients usually have a nephritic pattern with haematuria and red cell casts as the predominant feature.
Children - Minimal Change Disease (MCD)
Young adults - Focal Segmental Glomerular Sclerosis (FSGS)
Older people and most common overall - Membranous Nephropathy
Management of Nephrotic Syndrome?
Treat underlying pathology is always first step.
Conservative management:
Symptomatic improvement should usually be achieved with dietary sodium restriction
A high-protein diet (80 - 90 g protein daily)
increases proteinuria and can be harmful in the long term.
Prolonged bed rest should be avoided.
VTE stockings (Thrombo-Embolus Deterrent (TED) Stockings)
Pharmacological:
ACE inhibitors and / or angiotensin II receptor antagonists (AII-RAs). These drugs reduce proteinuria by lowering
glomerular capillary filtration pressure (a fall in efferent tone decreases the transglomerular capillary pressure, and so protein loss into the urinary space); blood pressure and renal function should be monitored regularly.
Loop diuretic (e.g. furosemide or bumetanide). Nephrotic patients may malabsorb diuretics (as well as other drugs) owing to gut mucosal oedema, and intravenous administration may be needed initially. Patients are sometimes hypovolaemic, and moderate oedema may have to be accepted to avoid postural hypotension.
LMWH (ex. Dalteparin)
Pneumococcal vaccine should be considered due to increased risk of Infection/sepsis.
Statin (lipid lowering)
Immunosuppressant (corticosteroid /Calcineurininhibitors - Ciclosporin or Tacrolimus/ Cyclophosphamide etc.)
Management of AKI?
_1. Find and treat causes (_e.g. sepsis, drugs, obstruction)
Bloods - FBC, U+Es, CRP, consider antibody screen if autoimmune cause suspected
Urine dip and microscopy
Bladder scan - if retention suspected
Ultrasound renal tract - if obstruction suspected
ECG - looking for hyperkalaemia/pericarditis
2. Stop renotoxic drugs
ACE-I/ARBs
Spironolactone
Diuretics
Gentamicin - may need dose adjustment if necessary for treatment
NSAIDs
3. Give IV fluid - aggressiveness depends on severity of AKI and comorbidities
Treat complications (e.g. hyperkalaemia, acidosis)
4. Give dialysis if:
Refractory hyperkalaemia
Severe acidosis (pH<7.2)
Refractory pulmonary oedema
Symptomatic uraemia (pericarditis, encephalopathy)
Drug overdose (e.g. aspirin)
Drugs to avoid in AKI (mnemonic)
DAMN
Diuretics
ACEi/ARB
Metformin
NSAIDs
What are the Pre-Renal/Intrinsic/Post-Renal causes of an AKI?
Pre-Renal:
Dehydration
Hypotension
Sepsis
NSAIDs
ACEi/ARBs
Over Diuresis
Renal artery stenosis
Renal artery thrombosis
Intrinsic:
Acute Tubular Necrosis
Myeloma
Glomerulonephritis
Vasculitis (SLE)
Acute Interstitial Nephritis
Nephrotoxic drugs
Tumour Lysis Syndrome
Post-Renal:
Bladder obstruction (Stone/tumour)
Prostate (BPH/Cancer)
Ureters (stone/stricture)
Blocked catheter
Retroperitoneal fibrosis
_____ is the most common* cause of *intrinsic acute kidney injury (AKI). It involves damage to the tubular epithelial cells within the renal tubules of the kidney due to either ____ or ____.
Acute Tubular Necrosis (ATN)
Ischaemia or direct toxicity
Clinical presentation
Acute kidney injury
Oliguria
Uraemia
Electrolyte imbalance
Causes
Ischaemic:
Hypotension
Shock
Haemorrhagic
Cardiogenic
Septic
Direct vascular injury
Trauma
Surgery
Nephrotoxic
Drugs:
Aminoglycocide antibiotics e.g. Gentamicin
Antifungal drugs e.g. Amphoteracin
Chemotherapy agents e.g. Cisplatin
Non-steroidal anti-inflammatory drugs e.g. Ibuprofen
Angiotensin converting enzyme inhibitors (ACEi) e.g. Ramipril
Angiotensin receptor blocker e.g. Candesartan
Statins
Contrast
Management
Correction of underlying cause
E.g. fluid resuscitation
Removal of nephrotoxins
May require haemofiltration or haemodialysis
