Theme 4 Lecture 4: Renal pathology Flashcards
What does erythropoietin do?
stimulates erythrocyte production
What does renin control?
fluid balance and blood pressure regulation (RAAS)
What is the presentation of acute renal failure?
- unwell, rapid rise in creatinine and blood urea (which are estimators of renal function)
- occurs over a few days
What is the presentation of nephrotic syndrome?
oedema, proteinuria, hypoalbuminaemia, haematuria, hypertension, renal failure
What is chronic renal failure?
slow decline in renal function
What is the kidney divided into?
outer cortex, inner medulla, renal sinus
What is found in the renal cortex?
glomeruli and tubules
What are podocytes?
cells in the bowmann’s capsule in the kidneys that wrap around capillaries of the glomerulus
What is the name for the functional unit of the kidney?
nephron
Why does the glomerulus lie between afferent and efferent arterioles?
because arteries have muscles in the vessel wall so they are able to maintain the volume and pressure of blood flow to maintain the function of ultrafiltration
What does the nephron consist of?
proximal convoluted tubule, loop of henle, distal convoluted tubule and collecting duct
What 3 factors can contribute to the narrowing of renal vessels
- hypertension
- diabetes
- atheroma e.g renal artery stenosis
What are the two conditions that can arise from vascular damage in the kidney?
- Thrombotic microangiopathy
- thrombi in capillaries/ arterioles
- endothelial damage by bacterial toxins, drugs, complement or clotting system abnormalities
e. g haemolytic uraemic syndrome - Vasculitis
- acute/chronic vessel wall inflammation with lumen obliteration
- various types affect different calibre vessels
e. g wegener’s granulomatosis
What are the immunological causes of glomerular damage?
- circulating immune complexes deposit in glomerulus e.g SLE/ IgA nephropathy
- circulating antigens deposit in glomerulus
- antibodies to BM/ glomerular components e.g goodpastures syndrome
How does immunological damage of the basement membrane lead to glomerular damage?
- immune complexes/antigens or antibodies deposit in glomerulus
- complement activation
- neutrophil activation
- reactive oxygen species
- clotting factors
- glomerular damage
What are the non-immunological causes of glomerular damage?
- endothelial injury e.g vasculitis, HTN, clotting disorders, HUS
- altered basement membrane e.g DM hyperglycaemia
- abnormal BM or podocytes due to inherited disease e.g alport disease
- abnormal protein deposition (amyloid) impair function e.g RA
Which ischaemic causes cause reduced perfusion and therefore tubular damage?
- hypotension e.g shock
- vessel damage e.g vasculitis, HTN
- glomerular damage
What are the toxic causes of tubular damage
-direct toxins
-hypersensitivity reactions - drugs
-crystal deposits e.g urate
-abnormal protein deposition e.g Ig’s
all of these cause inflammation of the tubular interstitial compartment
Which toxins can directly cause tubular damage?
- drugs e.g antibiotics, NSAIDs, ACEi, diuretics
- contrast medium
- organic solvents
- heavy metals
- ethylene glycol
- pesticides
What are some diseases of the kidney?
- Membranous nephropathy (primary/secondary)
- FSGS (primary/secondary)
- Mesangiocapillary glomerulonephritis minimal change disease
- Post-infective glomerulonephritis
- Anti-GBM disease
- IgA nephropathy
- Henoch-Schönlein purpura
- Lupus nephritis (in SLE)
What is mimimal change disease?
kidney disease where lots of protein lost in urine
What does crescentic mean?
rapidly progressive
What are the synonyms of glomerulonephritis?
nephropathy
glumerulopathy
nephritis
What are the features of nephrotic syndrome?
- damage to the glomerulus
- proteinuria (>3g in 24h)
- oedema
- hypoalbuminaemia
- +/- hypertension
- +/- hyperlipidaemia
- complications - infection, thrombosis
What are the causes of nephrotic syndrome in adults?
- membranous nephropathy (commonest)
- FSGS (focal segmental glomerulosclerosis)
- minimal change disease
- other causes - diabetes, lupus nephritis, amyloid
What are the causes of nephrotic syndrome in children?
- minimal change disease (ommonest)
2. FSGS
What are the features of acute nephritis?
- oedema
- haematuria
- proteinuria
- hypertension
- acute renal failure
What are the causes of acute nephritis in adults?
- post infective glomerulonephritis
- IgA nephropathy
- vasculitis
- SLE
What are the symptoms of vasculitis?
unwell, fever, rash, myalgia, arthralgia
What are the causes of acute nephritis in children?
- post infective glomerulonephritis
- IgA nephropathy
- henoch-schonlein purpura
- haemolytic uraemic syndrome
Who gets HUS and what are the symptoms?
typically children with E.coli 0157 enteritis
acute nephritis, haemolysis, thrombocytopenia
What are the signs and symptoms of acute renal failure?
- renal function degenerates rapidly in hours/weeks
- rapidly crescentic glomerulonephritis but not a specific disease
- anuria/oliguria
- raised creatinine and urea
- malaise, fatigue, nausea, vomiting, arrhythmias
- causes can be pre-renal, renal or post-renal
- prognosis is good if no underlying renal disease
Why would a patient with acute renal failure have arrhythmias?
electrolyte imbalance
What are the pre-renal causes of acute renal failure?
- reduced blood flow to kidney (most common)
- severe dehydration
- hypotension (bleed, septic shock, LVF)
What are the causes of post-renal acute renal failure?
urinary tract obstruction:
- urinary tract tumours
- pelvic tumour
- calculi
- prostatic enlargement
When can a renal biopsy be useful in diagnosing acute renal failure?
renal cause of acute renal failure e.g damage to kidney itself (not pre or post renal)
Which conditions lead to acute renal failure in adults?
- vasculitis
- acute interstitial nephritis (tubular damage with inflammation, usually due to drugs)
Which conditions lead to acute renal failure in children?
- PIGN (post infectious glomerulonephritis)
- Henoch-schonlein purpura
- HUS
- acute interstitial nephritis
what is another name for Henoch-schonlein purpura
IgA vasculitis
What are the complications of acute renal failure?
- cardiac failure (fluid overload)
- arrhythmias (electrolyte imbalance)
- GI bleeding
- jaundice
- infection esp. lung and urinary tract
What are the features of chronic renal failure?
- impaired renal function over a period of months or years
- permanently reduced GFR - reduced no. functional nephrons
- stage 4 and 5 usually require renal replacement therapy (dialysis or treatment)
What are the effects of chronic renal failure?
- reduced excretion of water/electrolytes: oedema, hypertension
- reduced excretion of toxic metabolites
- reduced production of erythropoietin: anaemia
- renal bone disease (impaired excretion of phosphate/calcium)
What is the commonest cause of chronic renal failure in adults?
diabetes
What is the commonest cause of chronic renal failure in children?
developmental abnormalities/malformations
What causes chronic renal failure in both adults and children?
- glomerulonephritis
- reflux nephropathy (repeated infections/scarring)
What is isolated proteinuria?
- proteinuria but less than nephritic range
- no allied haematuria, renal failure or oedema
- may be benign or due to renal disease
What are the causes of isolated proteinuria in adults and children?
adults: FSGS, DM, SLE
children: FSGS, HSP
What is isolated haematuria?
haematuria +/- proteinuria with normal renal function
-investigation needed to exclude malignancy
What are the causes of isolated haematuria?
- IgA nephropathy
- Thin basement membrane disease: inherited condition causing abnormally thin glomerular BM
- Alport hereditary nephropathy: inherited abnormalities of type IV collagen cause abnormal BM sometimes with eye and ear problems
What is pyelonephritis?
UTI where one or both of the kidneys become infected
What are the risk factors for acute pyelonephritis?
- female (ascending infection)
- instrumentation
- diabetes
- urinary tract structural abnormalities
What are the complications of acute pyelonephritis?
abscess formation
What are the risk factors for chronic pyelonephritis?
urinary tract obstruction/reflux
What are the complications of chronic pyelonephritis?
scarring, chronic renal failure
How does hypertension damage renal vessels?
wall thickening and reduction in lumen size
What are the two mechanisms of damage to the kidney due to hyperglycaemia?
- damaged basement membrane thickens and glomerulus produces excess extracellular matrix (nodules)
- small vessel damage causes ischaemia and tubular damage
What is myeloma
- plasma cell tumour
- excess Ig’s deposit in tubules cause inflammation and fibrosis
- renal tubule loss causes irreversible decline in renal function
Which disease shows a characteristic crescent when stained with H&E and looked at under a microscope?
anti-GBM disease - crescents represent cells proliferating in bowman’s capsule in response to any severe glomerular injury
