Glomerular Pathology and Clinical Presentations of Kidney Disease Flashcards
What are the 4 renal cortical ‘compartments’?
Glomerular
Tubular
Interstitial
Vascular
What are the 3 parts of the filtering mechanism?
Podocytes
Basement membrane
Endothelium
(Pathology can occur in any one of these)
What are the effects if the filter gets blocked?
Decreased GFR
Renal failure
What is nephrotic syndrome?
Loss of significant amounts of protein
(Mainly albumin)
Decreased oncotic pressure - oedema
What is nephritic syndrome?
Blockage of the glomerulus
Decreased GFR - AKI
Go into renal failure
Often haematuria and hypertension
If a patient presents with nephrotic syndrome, what is the likely site of injury?
Podocyte layer (Subepithelial)
What are the common primary causes of nephrotic syndrome?
Minimal change glomerulonephritis
Focal segmental glomerulosclerosis (FSGS)
Membranous glomerulonephritis
What are the common secondary causes of nephrotic syndrome?
Diabetes mellitus
Amyloidosis
Describe minimal change glomerulonephritis
Childhood/adolescence Incidence reduces with increasing age Heavy proteinuria/nephrotic syndrome Responds to steroids May recur Usually no progression to renal failure Glomerulus looks normal under a microscope - need electron An unknown circulating factor damages the podocytes
Describe FSGS
Nephrotic Glomerulosclerosis (scarred) Adults Less responsive to steroids Circulating factor damages podocytes Progressive to renal failure - dialysis needed
Describe membranous glomerulonephritis
Commonest cause of nephrotic syndrome in adults
Rule of thirds:
1/3 get better
1/3 stay the same
1/3 go onto end stage renal failure
Immune complex deposited - antigen attaches to podocytes then lots of IgG binds
Probably autoimmune but may be secondary
Describe the long term effects of diabetes mellitus on the kidneys
Kidneys get more and more leaky - progressive renal failure
Mesangial sclerosis - nodules that are easy to pick up histologically
Basement membrane thickening
Describe IgA nephropathy
Commonest glomerulonephritis Can occur at any age Classically presents with haematuria Relationship with mucosal infections Variable histological features and course \+/- proteinuria A significant proportion progress to renal failure No effective treatment
What are the 2 extremes of hereditary nephropathies?
Thin GBM nephropathy and benign familial nephropathy
To
Alport syndrome
Describe thin GBM nephropathy
Isolated haematuria
Thin GBM
Benign course
Describe Alport syndrome
X linked Abnormal collage IV Associated with deafness Abnormal appearing GBM Progresses to renal failure 'Basket weaving' abnormally split
Describe Goodpasture syndrome
Anti GBM disease
Relatively uncommon but clinically important
Rapidly progressive - acute onset of severe nephritic syndrome
Difficult to reverse
Association with pulmonary haemorrhage (high BP)
Autoantibody to collage IV in BM
What is the treatment for Goodpasture syndrome?
Immunosuppression Plasmaphoresis (give donor plasma to get rid of the autoantibody)
Describe vasculitis
Group of systemic disorders
No immune complex or antibody deposition
Association with anti-neutrophil cytoplasmic antibody (ANCA)
Nephritic presentation
Treatable if caught early
Urgent biopsy
Are kidney diseases painful?
Rarely
How do many kidney diseases present?
No symptoms
What is acidotic breathing?
Over-breathing
Trying to compensate for acidosis by blowing off more CO2
If patients say they are tired all the time, what investigations should be done?
FBC
Kidney function tests
What is uraemic syndrome?
Haemolytic anaemia
Acute kidney injury
Low platelet count
Very severe
How much extra water do you have to retain before getting peripheral oedema?
5L
What are some consequences of tubular dysfunction?
Impaired concentrating ability - increased frequency and nocturia
Acidosis
Glycosuria
Hormonal complications - metabolic bone disease because cannot activates vit D, anaemia due to lack of EPO and hypertension due to increased renin
Why do we usually urinate less frequently at night?
Urine is diurnally regulated
Concentrated more at night
Why might glycosuria present with tubular dysfunction?
Tubular disease causes a lower tubular threshold for glucose
Therefore may excrete glucose even when plasma glucose levels are normal
Who should be screened for kidney disease?
Hypertension Heart disease Diabetes Urinary tract obstruction Systemic disease (myeloma, lupus etc)
Give some causes of microscopic haematuria
UTIs Polycystic kidneys Renal stones Renal/bladder tumours Arteriovenous malformations Kidney/glomerular disease
What colour will blood be in from glomerular disease?
Brown/smoky in colour
Are clots in the blood in urine likely if from the kidneys?
No
Describe the blood in urine from glomerular disease
Brown/smoky in colour
Blood throughout stream
Painless
Clots are very unusual
Give some other causes of discoloured urine (brownish)
Haemoglobinuria
Myoglobinuria
Consumption of food dyes
What is the commonest glomerular cause of haematuria?
IgA nephropathy
What are red cell casts?
Binding of RBCs to a tubular protein that is always present in the urine
Why are there often dysmorphic RBCs in the blood?
Squeezed through the filtration barrier
What does urine with protein in it look it?
Frothy
Why are people with proteinuria more susceptible to infections?
Loss of immunoglobulins
Why are people with proteinuria in a pro-thrombotic state?
Increased risk of clotting due to imbalance of regulators of coagulation cascade
What is the classic triad of findings with nephrotic syndrome?
Proteinuria
Hypoalbuminaemia
Oedema
Why might you get hyperlipidaemia with nephrotic syndrome?
Disturbances to liver function
What extra-urinary signs suggest nephrotic syndrome?
Muehrcke’s bands - horizontal lines across the nails
Xanthelasma
Fat bodies in urine
Describe the manifestation of nephritic syndrome
Rapid onset Oliguria Hypertension Generalised oedema Haematuria Normal serum albumin Variable renal impairment Some proteinuria
What is required for a diagnosis of a nephritic syndrome?
Renal biopsy
How do nephritic and nephrotic syndromes different?
Nephrotic: More gradual onset More oedema Normal BP (raised in nephritic) Normal/low JVP More proteinuria Less haematuria Red cell casts usually absent Lower serum albumin
What is rapidly progressive glomerulonephritis?
Glomerular injury so severe that renal function deteriorates over days
May present as uraemic emergency
Associated with crescenteric glomerulonephritis
Antineutrophil cytoplasmic antibodies
Anti GBM antibodies
Often associated with systemic vasculitis
How is the glomerulus damaged in vasculitis?
‘Blown apart’ by inflammation in the blood vessels
Fibrin leaks out
Profound effect on filtration and tubular function
What are the pulmonary manifestations of vasculitis?
Opacities
Cavitation lesions
With CKD, under what eGFR do you have to be before symptoms occur?
< 30 ml/min
At what eGFR would we start patients on dialysis?
8 - 10 ml/min
Give some of the many symptoms of CKD
Tired/lethargic Breathlessness Nausea/vomiting Aches and pains Sleep reversal Nocturia Restless legs Itching Chest pains Seizures and coma
