Lecture 19 - Renal Pathology 2 Flashcards
What is the connotation of ‘chronic’ renal disease?
- Irreversible
* Long duration
What is the formal definition (in terms of GFR) of chronic renal failure?
GFR Less than 15mL / minute
What clinical condition often accompanies chronic renal failure?
Hypertension
What is the difficulty with clinical detection of chronic renal injury?
There is enormous renal function reserve: the other kidney
• Ability to survive with just one kidney
Thus CRF is often only detected late in the course
What is the macroscopic appearance of a kidney undergoing chronic renal failure?
No matter what the cause:
- Shrunken
- Scarred, fibrotic
- Pale (due to loss of glomeruli)
What are the clinical presentations of CRF?
- Asymptomatic
• Blood / urine test taken for various reasons - Symptomatic
• Anaemia
• Lethargy
• Anorexia / nausea
3. End stage renal failure • Coma • Pericarditis • Sepsis • Neuropathy
How is CRF assessed once it’s diagnosed?
Severity • GFR • Creatinine clearance • Kidney size • Haemoglobin (indicator of anaemia)
What are the causes of CRF?
2012:
35% Diabetic nephropathy
23% Glomerulonephritis
15% Hypertension
NB 15 years ago, Diabetic nephropathy and GN were in opposite positions
What are the treatment options for CRF?
Which has a better survival rate?
- Transplant
- Dialysis
Transplant has a 6-fold better survival rate than dialysis
NB There is a selection bias: people who are given transplants are likely to have better outcomes (children)
Describe how Diabetes Mellitus can lead to CRF
- Diabetic glomerulosclerosis / arteriosclerosis
- Infection → Pyelonephritis
- Papillary necrosis
What is pyelonephritis?
Caused by bacterial infection spread from:
• Urinary tract
• Circulation
Inflammation of kidney
How does DM-glomerular disease present?
- Proteinuria
- Nephrotic syndrome
- Deposition of glycosylated proteins in mesangium
- Slow control of glycaemia & BP
What is a Kimmelstiel-Wilson nodule?
Cardinal sign of DM-glomerular disease
• Collagen nodules forms in glomerular capillaries
What are some examples of chronic glomerulonephritis?
What is the commonest form?
- IgA nephropathy
- FSGS: Focal & Segmental glomerulosclerosis
- Lupus nephritis
IgA nephropathy is the most common form worldwide
Describe IgA nephropathy
How does it present?
Presence of predominantly IgA immune complexes in mesangium
In the past was though to be not so severe, but now is considered to be more severe
Majority of cases progress on to CRF
Presents as:
• Blood in the urine
• CRF
Describe FSGS
How does it present?
(Focal and Segmental Glomerulosclerosis)
Causes: Secondary to: • Obestiy • Infection • Hypertension 'Primary': • Circulating toxin that affects podocytes
Presents as:
• Heavy proteinuria
• Clinical nephrotic syndrome
Describe Glomerulonephritis in SLE
SLE:
• Multi system disease
• Frequent involvement of the kidneys
• Progression various greatly, some progresses to CRF
• Enormous immune complex load in the basement membranes in glomeruli
→ C’ activation; MAC formation
Define hypertension, and talk about it as a cause of CRF
Hypertension: chronically elevates systemic arterial BP
Nephrosclerosis:
• End result of longstanding HT
• Bilaterally shrunken, granular kidneys
• Larger scars
• Atheroma of larger arteries
• Sclerosis of arterioles
• Scarring of glomeruli and interstitium
Describe polycystic kidney disease
- Genetic basis
- Autosomal dominant
- Cysts in Liver, Pancreas & Kidneys
- Small aneurysms in brain
- Bilaterally huge kidneys
Which type of collagen is a major constituent in glomerular basement membranes?
Type IV collagen
Describe Alport syndrome
How does it present?
• Genetic mutation in gene for Type IV collagen
(most X-linked, fewer autosomal)
• Type IV collagen a major constituent in glomerular basement membrane
Presentation:
• Haematuria, not necessarily proteinuria. How bizarre
• Progressing deafness
• Ocular abnormalities
Progression to end stage renal failure
Describe Analgesic nephropathy
How does it present?
Longstanding use of 'compound analgesics' Containing: • Phenacetin • Caffeine • Aspirin
- Direct toxic effects of phenacetin metabolites
- & vascular effects
Presentation: • Bilaterally shrunken kidneys • Papillary necrosis • Calcification • Deteriation of renal function • Possible obstruction of ureter by sloughed off papilla
What are the radiological appearances of analgesic nephropathy?
- Swollen cortex
- Detachment
- Calcification
- Undulating outline
What is papillary renal necrosis?
Necrosis of renal papilla, which are supplied by the vasa recta
Renal papilla:
• Where medullary pyramids empty into minor calyces
At what point does CRF present?
Once damage is extensive
May take years to get to this point
What causes the anaemia of CRF?
EPO produced by kidneys
Decreased levels of EPO in body
Compare asymptomatic presentation in acute and chronic renal failure
Acute: picked up because we notice these things
Chronic: can be asymptomatic, and thus do not get picked up for years
Describe what happens to the following parameters in CRF:
• Size of the kidney
• Blood conc. of creatinine
Size: Shrinks progressively
When the kidneys are 50% shrunken, creatinine in the blood is not yet all that elevated
90% loss of kidney function: kidneys are tiny
• too late to treat CRF
What happens with renin in chronic renal failure?
Secretion of Renin
Activation of RAS → elevation of BP
Chronic hypertension is a cause of renal injury
This creates a vicious cycle
What is the commonest cause of chronic renal failure in Australia?
Diabetes mellitus
What is the effect of Diabetes mellitus on immunity?
DM decreases neutrophil function
DM patients are more prone to infection
Is Alport syndrome X linked or autosomal?
Most are X-linked
What was so bad about Phenacetin?
Caffeine + aspirin
Was supposed to be taken for a headache
The caffeine dependance caused headaches when not having Bex
People took these for everyday
→ Analgesic nephropathy
The compounds damage the medulla of the kidney (where the Loop of Henle dips down)
• Microvasculature affected
What is the pathogenesis of analgesic nephropathy?
Direct toxic & vascular effects of the analgesic metabolites
What is the inheritance of polycytic kidney disease?
Autosomal dominant
What is the typical pathological feature of DM-glomerular disease?
Kimmelstiel-Wilson nodule
