medical renal pathology Flashcards
what is the role of the kidneys?
to eliminate metabolic waste products, to produce hormones, to regulate fluid or electrolyte balance and to regulate the acid base balance
what hormones does the kidney produce?
renin for fluid balance in RAAS
erythropoeitin for erythrocytes
what is the prevalence of renal disease?
26000 patients per year get acute renal failure in England which account for 15% of all hospital admissions - most will recover but 10000 will need dialysis with a 50% mortality
5500 patients will develop chronic renal failure per year and there are around 43000 cases in England - 50% will have transplant, 40% haemodialysis and 10% peritoneal dialysis
what is the RAAS?
the renin angiotensin aldosterone system
the adrenals release aldosterone. This acts on the kidney to reduce water and sodium excretion and increase potassium excretion. Therefore there is vasoconstriction of blood vessels, increased extracellular fluid volume, effective circulating volume and blood pressure due to Na and H2O, there is also decreased plasma K due to loss of K+. The increase in volumes and BP leads to a decrease in renin (also produced by the adrenals). Therefore there is lerss angiotensin I and II (I-II in lungs by ACE), therefore thirst and ADH decrease. Therefore the hypothalamus releases less corticotropin releasing hormones from pituitary gland meaning that there is less stimulation to the adrenals - negative feedback so less aldosterone produced.
where can donors be sourced?
they can be living or deceased
how will renal disease present?
acute renal failure - unwell due to rapid rise in creatinine and urea, nephrotic syndrome with hypoalbuminaemia, proteinuria and oedema
acute nephritis - oedema, proteinuria, haematuria, hypertension and renal failure
chronic - slow decline in renal function with haematuria and proteinuria
what is diagnosis of renal disease based on?
renal physician - clinical history and examination
radiologist - obstruction, size and structural abnormalities
biochemist - blood tests (urea and creatinine) and urinalysis (protein, blood and electrolytes)
urologist - cystoscopy - obstruction and haematuria
pathologist - renal biopsy - immunofluorescence, light and electron microscopy
what is the glomerulus?
coiled capillary with podocytes covering it. The filter is the podocytes foot processes, endothelial cells and basement membrane
what is the blood flow through the kidney?
branches of the renal artery flow into the afferent arteriole and through the glomerulus and then through the efferent arteriole up to the branches of the renal vein
from the bowmans capsule what is in a nephron?
the capsule leads into the proximal convoluted tubule, down into the descending limb, loop and ascending limb of henle, then into the distal convoluted tubule into the collecting dict to the pelvis of the kidney
what does a nephron span?
the renal cortex (above limbs of henle) and the renal medulla (below LoH)
what are some causes of kidney failure?
tubular, glomerular and vascular damage
outline vascular damage?
there can be thrombotic microangiopathy. This is when there are thrombi in the arterioles or capillaries and therefore there is endothelial damage by bacterial toxins, drugs, complement or clotting system abnormalities. This will lead to haemolytic uraemic syndrome.
There can also be vasculitis where there is acute or chronic vessel wall inflammation with lumen obliteration. There can also be various types affecting different calibre vessles such as in Wegeners granuomatosis
what else contributes to vascular damage?
hypertension, diabetes or atheroma such as in renal artery stenosis
how can glomerular damage occur?
through immunological or non immunological causes
what are the immunological causes of glomerular damage?
circulating immune complexes that deposit in the glomerulus such as in SLE
circulating antigens deposit in the glomerulus
antibodies to BM or glomerular components such as in Goodpastures
this results in complement and neutrophil activation, reactive oxygen species and clotting factors leading to damage
what are the non immunological causes of damage?
endothelial injury such as vasculitis
altered basement membrane such as in DM hyperglycaemia
abnormal BM podocytes due to inherited disease such as Alport
abnormal protein deposition (amyloid) impairing the function such as in myeloma
this results in basement membrane and vessel damage and therefore glomerular damage
what is the issue with diagnosis of renal disease?
the aetiology and pathophysiology may be unclear
conditions relate to histological appearances but more than one disease may look the same, some diseases have variable histology, some names are both diseases when idiopathic and appearances when secondary to known cause
what are the causes of tubular damage?
ischaemic or toxic
what is ischaemia causes of tubular damage?
hypotension due to shock etc
vessel damage due to vasculitis or HTN
glomerular damage
this leads to reduced perfusion and tubular damage
what are the toxic causes of tubular damage?
direct toxins
hypersensitivity reactions from drugs
crystal deposits such as urate
abnormal protein deposition
what determines the degree of renal function?
it correlates with the degree of renal tubule damage
what are direct toxins?
pesticides, ethylene glycol, drugs, heavy metals, contrast medium and organic solvents
what are the conditions that will lead to blood vessel damage?
inflammatory - vasculitis
endothelial damage - hypertension, thrombotic or microangiopathy
abnormal deposits - amyloid or diabetes
what are the conditions that will lead to damage to glomerulus?
immunological - membranous nephropathy, antiGBM disease, IgA nephropathy, SLE or post infective glomerulonephritis
non immunological - minimal change disease or FSGS
what are the conditions that lead to damage to the tubule?
direct toxicity - drugs and poisons such as gentamicin
hypersentivity to drugs
inflammatory - pyelonephritis or sarcoid
ischaemic - shock. glomerular damage or vascular disorders
abnormal deposits - myeloma
what is nephrotic syndrome caused by?
always due to damage to the glomerulus
what is the presentation of nephrotic syndrome?
hypoalbuminaemia, proteinura (>3g in 24 hours), oedema, maybe hyperlipidaemia and hypertension
what are the complications of nephrotic syndrome?
infection or thrombosis
what are the conditions that cause glomerular damage and lead to nephrotic syndrome in adults?
minimal change disease
focal segmental glomerulosclerosis
membraneous nephropathy - commonest
what is the epidemiology of membranous?
usually adults <60 years and more males than females
20-30% will progress to end stage renal failure
what are the causes of FSGS?
various - usually idiopathic but also genetic and in heroin use and HIV
males more than females
what is the presentation of minimal change?
male and female equal
normal histology
diabetes, lupus and amyloid
what are the conditions that cause glomerular damage and lead to nephrotic syndrome in children?
FSGS or minimal change
other causes are very rare
what is the prognosis of minimal change in children?
excellent
what are the clinical effects of acute nephritis?
oedema, haematuria, proteinuria, hypertension and acute renal failure
what are the conditions that cause acute nephritis/ nephritic syndrome in adults?
IgA nephropathy, SLE, post infective glomerulonephritis, vasculitis
what can cause PI glomerulonephritis?
streptococcal throat infection - good recovery
what are the effects of IgA nephropathy?
it is a common primary glomerular disease in young adults but 20-50% have renal failure over 20 years
what is the presentation of vasculitis?
unwell, fever, rash, myalgia and arthralgia
what is SLE and who does it usually affect?
young women
autoimmune disease
what are the conditions that cause acute nephritis/ nephritic syndrome in children?
IgA nephropathy
PI glomerulonephritis
henoch-schonlein pupura
haemolytic-uraemic syndrome
what is HSP?
specific IgA nephropathy resulting in systemic vasculitis
often follows a throat infection and most will recover completely
usually teenage boys with arthralgia, abdo pain, purpuric rash, protein/haematuria, ARF
how does HUS present and what causes it usually?
acute nephritis, haemolysis, thrombocytopenia, typically children with E coli 0157 enteritis
what are the three causes of ARF?
pre, post and renal failure
why does pre renal lead to ARF?
most commonly there is reduced blood flow to the kidney due to severe dehydration or hypotension and therefore a renal biopsy will be unhelpful
in which cause is a renal biopsy helpful?
renal causes - damage to the kidney itself
what is post renal causes of ARF?
urinary tract obstruction due to pelvic tumours, calculi, prostatic enlargement or UT tumours
what is the presentation of ARF and effects?
anuria or oligura (<400ml/24hrs), raised creatinine and urea resulting in nausea, vomiting, arrhythmias, fatigue and malaise as well as acute tubular necrosis
what is the prognosis of ARF?
good if not underlying renal disease but short term dialysis may be needed in some patients
what are the causes of ARF in adults commonly?
vasculitis or acute interstitial or tubulointerstitial nephritis
what is tubuloinsterstitial nephritis?
tubular damage with inflammation, usually due to drugs but most recover
what are the main causes of ARF in children?
PIGN, HSP, HUS, and AIN
what is not a specific disease and is rapidly progressive crescentic glomerulonephritis?
acute nephritis with acute renal failure
what are the complications of ARF?
cardiac failure - fluid overload arrhythmias - electrolyte imbalance GI bleed - multifactorial jaundice - hepato venous congestion infection - usually urinary or lung
what is the treatment of ARF?
depends on the underlying cause
short term dialysis
what is chronic renal failure?
it is a permanently reduced GFR with a reduced number of functional nephrons - it is rated from stages 1-5
outlines the stages of CRF?
1 - normal GFR - >90ml/min/1.73m^2 2 - mild - 60-89 3 - 30-59 - moderate 4 - severe - 15-29 5 - failure - <15 or dialysis
what will end stage kidney disease show and why is a biopsy unhelpful?
we already know the clinical effects so unnecessary
kidney show severe scarring with loss of glomeruli and tubules
what are the effects of CRF?
reduced excretion of water and electrolytes - oedema and HTN
reduced excretion of toxic metabolites
reduced production of erythropoeitin - anaemia
renal bone disease - phosphate or calcium
what are the main chronic conditions that lead to CRF?
adults - diabetes
adults and children - glomerulonephritis, reflux nephropathy
children - developmental abnormalities or malformations
what is reflux nephropathy?
repeated infections or scarring
what are the characteristics of isolated proteinuria?
it is proteinuria but less than the nephrotic range - there is no allied haematuria, renal failure or oedema, it may be benign or due to renal disease
what are the causes of isolated proteinuria in children and adults that may be from renal disease?
in adults FSGS, DM, SLE
children - FSGS, HSP
what are the benign causes of proteinuria?
exercise, postural or related to pyrexia
what is isolated haematuria?
it is haematuria with or without proteinuria with normal renal function
what are the causes of isolated haematuria?
IgA nephropathy, thin basement membrane disease, alport disease
what is needed in isolated haematuria?
urology or cytology to exclude a malignancy
what is thin basemen membrane disease?
it is an inherited condition that causes abnormally thin glomerular BM but the renal function is usually normal
what is alport nephropathy?
it is hereditary nephropathy - inherited abnormalities of the type IV collagen causing abnormally thin BM, sometimes with eye or ear problems resulting in renal failure, deafness or occular problems
what is renal artery stenosis and the result?
it is thinning of the renal artery most commonly due to atheroma or arterial dysplasia. There is ischaemic injury of the affected kidney and activation of the RAAS leading to HTN. There is loss of renal tissue leading to renal function reduction
what are the risk factors for acute pyelonephritis and what are the complications?
the risk factors are being female - ascending infection risk, instrumentation, diabetes, urine tract abnormalities and the complications are abscess formation
what are the risk factors and complications of chronic pyelonephritis?
the risk factors are urinary tract obstruction or reflux
complications are scarring and chronic renal failure
how does infection commonly spread in the kidney?
haematogenous spread
what are the characteristics of vasculitis?
there are various types that affect different calibre vessels and the inflammation in the glomerular vessels can cause clotting and obliteration of the capillary lumena and glomerulus destruction. The inflammation of the larger renal arterioles can cause tubule hypoxia. It is usually associated with systemic infection with a rash, arthralgia, fever, malaise, myalgia and weight loss
what is the course of hypertension with regards to renal function loss?
the HTN will damage the renal vessels so there is wall thickening and lumen narrowing. This produces chronic hypoxia - loss of renal tubules and reduced renal function. The reduced renal blood flow activates the RAAS resulting in exacerbation of the HTN
how does diabetes affect renal function?
it is the commonest cause of end stage renal failure in the developed world. There are two mechanisms of damage due to hyperglycaemia. The damaged BM thickens and the glomerulus produces excess ECM resulting in nodules and the small vessel damage cause ischaemia and tubular damage
what is myeloma?
it is a plasma cell tumour that results in excess Ig deposits in the tubules causing inflammation and fibrosis, the renal tubule loss causes irreversible damage and decline in renal function
where are you most likely to see myeloma?
in an elderly patient with acute renal failure once have excluded drug reactions
what is most of the thickness of the capillary wall?
the BM
which cells maintain glomerular structure?
mesangial cells
how will thrombosis be detected?
in histology there will be bright pink areas which are fibrin - thrombosis in the glomerulus and capillary lumena are obliterated
inflammatory cells will surround the artery wall that is damaged
how will myeloma show in histology?
there will be smooth pink thick walls of arteries that show Ig deposits, the bright pink tubules are destroyed due to Ig and there will be signs of fibrosis
how will a glomerulus appear in histological stain of membranous nephropathy?
thickened glomerular capillary walls
in FSGS how will the glomerulus appear?
mostly normal bar a solid area with loss of capillary lumena
in PIGN and IgA nephropathy how will the glomerulus appear?
both will show the glomeruli with increased cellularity and loss of capillary lumena
how will acute tubulointerstitital nephritis appear in histology?
renal cortex - between renal tubules there will be dark dots - these are many inflammatory cells or lymphocytes
how will anti GBM disease appear in histology?
glomerulus - crescents which show the proliferating bowmans capsule, in response to any severe glomerular injury such as PIGN or vasculitis
how will acute tubular necrosis show in histology?
there will be a loss of nuclei from tubular cells - cell death
what will show chronic kidney damage in a histology?
there will be interstitial damage and tubular atrophy
atrophic tubules, chronic damaged shrunken tubules that are surrounded by fibrosis - end stage
next to residual normally closely packed tubules
