Urinary: Pathology Flashcards
Which areas can pathology in kidney affect?
- Glomerulus
- Tubular compartment
- Interstitium
- Vascular
What can the glomerular filter leaking cause?
- Proteinuria
- Haematuria
One or both
What is area of the glomerulus is affected in nephrotic syndrome?
Podocyte/Sub-epithelial damage
How is nephrotic syndrome managed?
Oedema - Salt and fluid restriction, diuretics
Proteinuria - ACE inhibitors
Hypercholesteraemia - Statins
Treat the underlying cause
What are the common primary causes of nephrotic syndrome?
- Minimal change glomerulonephritis
- Focal segmental glomerulosclerosis
- Membranous glomerulonephritis
What are the features of minimal change glomerulonephritis?
- Usually arises in childhood and adolescence.
- Responds to steroid but may recur if the steroid are stopped
- Doesn’t usually progress to renal failure
What is minimal change glomerulonpehritis?
- Damage to podocyte layer so patient can’t selectively filter so proteins pour out of the glomerulus.
- Thought to be immune associated
What is focal segmental glomerulosclerosis?
- Damage to podocyte layer so patient can’t selectively filter so proteins pour out of the glomerulus.
- Heals by scarring after being damaged by circulating factors in the blood (haven’t found out which it is)
What are the features of focal segmental glomerulosclerosis?
- Scarring of the glomerulus occurs
- Less effectively treated by steroids
- Progression rapidly to renal failure
- Patients can get FSGS even after they have a kidney transplant
What is membranous glomerulonephritis?
- Autoimmune
- Immune complex deposits on sub-epithelial layer causing damage to the podocyte layer
What are the features of membranous glomerulonephritis?
- Rule of thirds
- Commonest in adults
- May be secondary for example lymphoma
What are secondary causes of nephrotic syndrome?
- Amyloidosis
- Diabetes Mellitus
What are the pathological changes that occur in diabetes mellitus?
- Hyperfiltation/Capillary hypertension
- Glomerular basement membrane thickening Mesangial expansion
- Podocyte injury
- Glomerular sclerosis
Why does hyperfiltation/capillary hypertension occur in diabetes mellitus?
Occurs in early course of disease.Related to hyperglycaemia
- Increase in glucose levels
- Upregulates SGLT2 transporter
- Less glucose passed out in urine
- Increase in reabsorption of sodium
- Less sodium gets to the macula densa
- Less effect on JGA
- Afferent vasodilation
- Efferent vasoconstriction
- Glomerular hypertension occurs as a result
- GFR increases
What are the risk factors for diabetes mellitus?
- Genetic susceptibility
- Race
- Hypertension
- Hyperglycaemia
- High level of hyper-filtration
- Increasing age
- Duration of diabetes
- Smoking
What are the stages of of diabetic nephropathy?
- Hyperfiltration and hypertrophy
- Latent stage
- Microalbuminuria
- Overt proteinuria
- ESRD
What happens in the latent stage of diabetic nephropathy?
- Normal albuminuria
- GBM thickening and mesangial expansion
What happens in the microalbuminuria stage of diabetic nephropathy?
- Variable mesangial expansion/sclerosis
- Increase GBM thickening
- Podocyte changes
- GFR normal
What happens in the overt proteinuria phase of diabetic nephropathy?
- Diffuse histopathological changes
- Systemic hypertension
- Falling GFR
- Mesangial expansion/sclerosis leads to reduced surface area for filtration
- Microvascular changes (hyalinosis of arterioles) leads to tissue ischaemia
What is the primary prevention of diabetic nephropathy?
- Tight blood pressure control
- SGLT2 inhibitors (Reduced hyper-filtration)
- Statin therapy
- Cardiovascular risk management (diet, exercise)
- Moderate protein intake
How is diabetic nephropathy managed?
- Hyper-filtration & hypertrophy – primary prevention
- Latent stage – primary prevention
- Microalbuminuria -RAAS Blockage to reduced glomerular hyper filtration. Hyperkalaemia limits use with advanced CKD
- Overt proteinuria
- ESRD
What are the clinical features of hypertensive renal disease?
- Microalbuminuria is the first sign
- Slow and progressive
- Disease of exclusion (no evidence of hypertensive disease elsewhere)
What is the management of hypertension renal disease?
- Slow progression
- Good BP control
- ACE inhibitors or angiotensin receptor blockers with albimunuria
What are the histoligcal changes that occur in hypertensive nephrosclorosis?
- Vascular changes
- Fibro-elastic intimal thickening leading to lumen narrowing
- Hyalinosis of the afferent arterial wall (diabetes affects efferent as well)
- Secondary insult causing glomerular changes such as wrinkling of glomerulus and glomerulosclerosis
- Leads to CKD
What is renal disease associated with acute severe hypertension?
- Damage to endothelium leading to haematuria
- Activation of RAAS
- Glomerulus is punched out so acute kidney injury.
- Fibrinoid necrosis of arterioles so ischaemia which leads to activation of RAAS
- Haemolytic anaemia due to shearing of blood vessels
- Associated with Scleroderma and Haemolytic uraemic syndrome
- Leads to AKI
What are the differentiating factors between hypertensive renal disease and renal vascular disease?
- Hypertension is often more acute in renal vascular disease and refractory to treatment
- Decline in GFR often more rapid
- Evidence of atherosclerosis elsewhere
- Acute worsening with RAAS blockade leads to reduction in GFR even more as kidney thinks its hypovolaemia
What are the primary features of nephritic syndrome?
- Loss of protein
- Blood in urine
- Acute renal failure usually
- Hypertensive
- Low GFR
How is nephritic syndrome managed?
- Blood pressure control
- Treatment of oedema
- Cardiovascular risk management
- Disease specific treatment such as immunosuppressant
What are the conditions that cause nephritic syndrome?
- Anti-GBM disease
- Vasculitis
What are the site affected by glomerular injury?
- Basement membrane
- Podocyte
- Sub-epithelial
- Sub-endothelial
What are the causes of haematuria?
Blood vessels are commonly injured
Non nephrological
- IgA Nephropathy
- Thin glomerular basement membrane nephropathy
- Hereditary Nephropathy (Alport)
Cancer
- Renal cell carcinoma (RCC)
- Upper tract transitional cell carcinoma (TCC)
- Bladder cancer
- Advanced prostate carcinoma
Other causes
- Stones
- Infection
- Inflammtion
- Benign prostatic hyperplasia
How is IgA nephropathy managed?
- Can detect abnormal IgA
- No effective treatment. ACE inhibitors can slow it down but not that underlying cause
What is IgA nephropathy?
- Commonest glomerular membrane
- IgA is naturally secreted into mucosal membrane. IgA deposited in the kidney. If you get infected you produce more IgA.
- IgA is deposited in the mesangium as there is nothing to stop it getting into the mesangium
- Causes the capillary loop to become fragile as a result which leads to haematuria (visible/invisible)
- Can also get protein in urine
What are the features of thin glomerular basement membrane nephropathy?
- Doesn’t progress
- Benign
What is Hereditary Nephropathy (Alport syndrome) ?
- X-linked
- Abnormal collagen 4
- Associated with deafness as collagen 4 is used in the ear
- Abnormal appearing glomerular basement membrane
- Progress to renal failure
What are the symptoms of chronic kidney disease?
- Fatigue / malaise
- Loss of appetite / Loss of weight
- Acute illness / recent infection
- Ankle swelling
- Haematuria / nocturia
What are the symptoms of acute kidney disease?
- Dysuria
- Change in urine –amount / colour
- Pain (supra-pubic / loin / joints)
- S/E of drugs with renal metabolism
- Nausea & vomiting
- Ankle swelling / SoB
- Fatigue / Malaise
- Fever
What are risk factors of acute kidney disease?
- Ishaemic heart disease
- Hypertension
- Cerebrovascular disease
- Known CKD (risk factor for AKI)
- Diabetes mellitus
- In younger patient – enuresis in childhood, problems in pregnancy
What examination are undertaken for acute kidney disease?
- Blood pressure
- Urine dipstick
- Urine microscopy if dipstick positive
