Pathology of the urinary tract Flashcards
Erythropoietin - funtion
Produced in response to ↓ oxygen tension → stimulate maturation of erythrocytes in the bone marrow.
Calcitriol (activated vitamin D) - function
Facilitates Ca absorption in the small intestine.
pre-renal failure - causes
Secondary to circulatory collapse (shock, hypovolaemia) or local obstruction of vascular supply (thrombus or lodgement of embolus)
renal failure - causes
Tubular necrosis - infectious agents, toxins and toxic metabolites, nephrotoxic drugs and chemicals.
Embolic disease or ascending pyelonephritis
post-renal failure - causes
Ascending infection, urolithiasis or neoplasms
acute renal failure
Occurs when >75% of renal functional capacity is abruptly impaired.
Failure to excrete waste products and to maintain fluid and electrolyte homeostasis
acute renal failure effects
Abrupt decr in serum concentrations of urea + creatinine (azotaemia)
nitrogenous waste products of protein catabolism - indices of diminished renal function.
Retention of K+ - cardiac dysrrhythmia (& arrest).
Retention of phosphates - binds ionised calcium (hypocalcaemia) - muscular tremors & coma.
Disturbances of electrolytes and ↓ pH - metabolic acidosis.
Hypertension.
Oliguria/anuria
chronic renal failure
insufficient glomerular filtration - progressive
retention of nitrogenous metabolites
failure of tubular function
chronic renal failure - effects
progressive salt and water retention, metabolic acidosis, other electrolyte imbalances (esp hyperkalaemia)
decr phosphates - secretion - hyperphosphataemia & Ca2+ precipitation, decr active Vit D3 (calcitriol)
hypertension
Chronic renal disease - clinical signs
Polyuria, isosthenuria, polydipsia, etc
Halitosis, dribbling, lank coat, loss of weight
older cats & dogs
CRF - histological appearance
incr of interstitial connective tissue.
Renal tubules absent, atrophic or compressed.
Hyperplastic + hypertrophic tubules.
Intraluminal protein.
Thickened hyalinised basement membranes.
Calcification of vessels and basement membranes.
Multiple acquired cysts.
Glomerulosclerosis.
Foci of interstitial lymphocytes and plasma cells
end stage renal failure - kidney appearance
replacement of renal parenchyma with mature fibrous tissue
Kidneys are firm and distorted.
Distortion due to contraction of mature fibrous tissue (scarring)
uraemia - define
urea in the blood
4 stages of developing uraemia
- decr renal reserve, GFR 50% asymptomatic
- Renal insufficiency, GFR is 20-50% azotaemia + polyuria
- Renal failure, GFR 20-25% , kidneys can not maintain
homeostasis, uraemia (GI, cv, respiratory and skeletal
complications). - End-stage renal disease, GFR <5% terminal uremia.
Systemic Effects of Uraemia
retention of nitrogenous metabolites.
NaCl and water retention, metabolic acidosis, other electrolyte imbalances (esp hyperkalaemia).
Plasma protein loss (oedema).
Hyperphosphataemia and secondary renal hyperparathyroidism.
↓ Production of erythropoietin → ↓ stimulation of erythropoietic maturation → non-regenerative anaemia.
Hypertension.
Secondary Renal Hyperparathyroidism due to uraemia - chain of events
GFR <25% phosphate is no longer adequately secreted by the kidneys.
Hyperphosphataemia precipitates ionised calcium conc in serum.
decr calcitriol - decr intestinal absorption of calcium.
decr ionised serum Ca stimulates PTH secretion - Ca
release via osteoclastic bone resorption.
try to incr renal excretion of phosphate + reabsorption of Ca.
Parathyroid chief cell hyperplasia - renal secondary
hyperparathyroidism.
Secondary Renal Hyperparathyroidism - effects - kidneys
Fibrous osteodystrophy and mineralisation of soft tissues.
Renal disease made worse by nephrocalcinosis - calcification of tubular BMs, Bowman’s capsules and necrotic tubular epithelium
Secondary Renal Hyperparathyroidism - effects - non-renal
Endothelial degeneration and necrosis - vasculitis with
secondary thrombosis and infarction
mineralisation
ulcers
examples of non-renal lesions due to Secondary Renal Hyperparathyroidism
Caustic injury to epithelium of the oral cavity and stomach (ulceration) Ulcerative glossitis and stomatitis Ulcerative and haemorrhagic colitis Ulcerative and haemorrhagic gastritis Uraemic encephalopathy Uraemic pneumonitis + Pulmonary calcification Intercostal mineralisation Fibrinous pericarditis Arteritis
portals of entry to the kidney
haematogenous
glomerular infiltrate
ascending from the ureter
direct penetration
main Diseases of the Glomeruli
Immune mediated glomeruolonephritis.
Glomerular Amyloidosis
Acute suppurative glomerulitis
Glomerulosclerosis
Causes of glomerular damage
Damage tofiltration barrier - deposition of immune complexes. thromboemboli and bacterial emboli. Direct viral or bacterial infection Damage to other parts of the nephron. Reduced blood flow. Chronic loss of tubular function. Amyloid deposition.
Functions of the glomerulus affected
Plasma ultrafiltration. Blood pressure regulation. Peritubular blood flow regulation. Tubular metabolism regulation. Circulating macromolecule removal
Protein losing nephropathy
albumin leaks into filtrate - too much protein to be absorbed in PCT
high protein filtrate in dilated tubular lumina - proteinuria and hypoproteinaemia
renal protein loss - decr plasma colloid osmotic pressure + loss of antithrombin III - nephrotic syndrome
nephrotic syndrome
generalised oedema, ascites, pleural effusion, hypercoagulability and hypercholesterolaemia
Responses of glomeruli to injury
Necrosis. Proliferation of cells and membranes. Infiltration of leukocytes. decr vascular perfusion. Incr vascular permeability
response of glomeruli to continued/severe injury
atrophy and fibrosis of the glomerular tuft (sclerosis) and secondarily atrophy of renal tubules
Immune mediated glomerulonephritis - how it happens
Circulating immune complexes in subepithelial,
subendothelial or mesangial locations.
antibodies against entrapped nonspecific antigens or
antigens within the GBM.
release of proteineases and oxygen derived free
radicals - damage the basement membrane.
Activation of both glomerular epithelial cells and mesangial cells to produce damaging mediators such as oxidants and proteases
Immune mediated glomerulonephritis - causative diseases
persistent infections
Specific viral infections → FeLV and FIP.
Chronic bacterial infection → pyometra or pyoderma.
Chronic parasitism.
Autoimmune diseases such as SLE.
Neoplasia
Transient infection
Continual exposure of glomeruli to soluble IC
Immune mediated glomerulonephritis - diagnosis
IF or IHC of immunoglobulin + complement components in the glomerular tufts.
specific causative antigen often hard to identify
electron dense deposits in mesangial, subepithelial
or subendothelial locations by EM
Immune mediated glomerulonephritis - gross appearance on kidneys
Glomeruli visible as pinpoint red/pale dots on the cut surface of the cortex.
Fine granularity to the cortical surface.
Capsule may be adherent.
Immune mediated glomerulonephritis - histopathology
↑ cellularity + proliferation of glomerular cells.
Dilated renal tubules filled with homogenous proteinaceous fluid.
Interstitial and periglomerular fibrosis.
Foci of interstitial lymphocytes & plasma cells.
Glomerulosclerosis.
Glomerular Amyloidosis
associated with chronic inflammatory disorders, systemic infectious disease or neoplasia.
deposits - fragments of a serum acute phase reactant protein.
Glomeruli are the most common renal sites for deposition
of amyloid.
Idiopathic.
Glomerular Amyloidosis - consequences
PLN and the nephrotic syndrome
decr RBF through the glomeruli and the vasa recta
tubular atrophy, degeneration and fibrosis. In severe cases
renal papillary necrosis.
Medullary amyloidosis is usually asymptomatic unless papillary necrosis.
Glomerular Amyloidosis - gross appearance on kidneys
Enlarged, pale, smooth to finely granular capsular surface
Amyloid laden glomeruli may be visible as fine glistening dots on the cut surface of the cortex.
Brown staining of glomeruli after treatment with iodine.
Medullary amyloidosis not grossly visible
Glomerular Amyloidosis - histopathology
Glomerular amyloid in mesangium and subendothelium.
Acellular eosinophilic homogenous to fibrillar material.
tubules - dilated and contain proteinaceous and cellular casts
stains with Congo red - amyloid deposits have
apple green birefringence under polarised light
Acute suppurative glomerulitis - cause
bacterial or embolic nephritis.
Bacteraemia - bacteria in glomerular and interstitial capillaries
formation of microabscesses in cortex.
glomeruli are targeted but manifestation of renal vascular disease
Produce toxic by products → damage endothelium →
localised vasculitis and colonisation → embolic nephritis
Acute suppurative glomerulitis - bacterial causes
Actinobacillus equuli in foals.
Erysipelothrix rhusiopathiae in pigs.
Corynebacterium pseudotuberculosis in sheep and goats.
Arcanobacterium pyogenes in cattle
Acute suppurative glomerulitis - gross appearance on kidneys
Multifocal random raised tan pinpoint foci - subcapsular and cut surface of renal cortex.
Acute suppurative glomerulitis - histopathology
Glomerular capillaries - bacterial colonies admixed with necrotic debris and neutrophils.
Glomerular or interstitial haemorrhage.
Can persist as focal residual abscesses
or progressively replaced by chronic
inflammation and coalescing scars.
Glomerulosclerosis
↓ in the no. of functional glomeruli.
Loss of glomerular capillaries + replacement of mesangial matrix and Bowman’s space by FCT.
↓ blood flow through the vasa recta from glomerular efferent arteriole.
hypoxia → tubular epithelial degeneration and loss.
Chronic proteinuria.
Diseases of the Tubules
Inherited Abnormalities, Acute Tubular Necrosis
Causes of tubular disease
Blood borne infections Ascending infections (intratubular pathogens). Direct damage from toxins (intratubular effects). Ischemia. Infarction. Tubular obstruction. Interstitial fibrosis. External compression
Responses of the tubules to injury
Degeneration, necrosis, apoptosis and/or atrophy → PCT most vulnerable.
Cells slough into the lumen to form cellular casts.
compensatory hypertrophy → attempt to maintain overall renal function
no regeneration of nephrons
Responses of the tubular basement membrane to injury
retained more consistently after toxic rather than ischemic results.
if it remains intact → repair by proliferation of the remaining viable epithelial cells.
Severe damage to or loss of tubular basement membranes → necrosis, failure of functional repair and replacement by fibrosis.
Primary renal glycosuria
Inherited disorder
decr reabsorbtion of glucose by tubular epithelial cells
no gross or histological findings.
Predisposes to bacterial infections of LUT
Fanconi syndrome
hereditary defect in tubular reabsorption of protein, glucose, phosphate, amino acids.
Can develop progressive renal insufficiency & associated renal fibrosis.
cystinuria
Sex linked inherited tubular defect in male dogs
predisposes to calculus formation and obstruction of the LUT.
acute tubular necrosis - effect
decr renal perfusion → ↓ GRF & activation of arteriolar vasoconstriction → prolonged ischemia
Nephrotoxic pigments - Haemoglobinuric nephrosis - causes
chronic copper toxicity in sheep, babesiosis in
cattle, red maple toxicity in horses and AIHA in dogs.
Nephrotoxic pigments - Myoglobinuric nephrosis
extensive muscle necrosis
azoturia of horses, capture myopathy of exotic or wild
animals and severe trauma.
Acute Tubular Necrosis - Heavy metals
Lead → membrane/mitochondrial damage in the PCT cells
Acid fast IN inclusions present in the PCT epithelium
specific metal can’t be identified by renal lesions alone
Acute Tubular Necrosis - oak poisoning in cattle
toxic substances are metabolites of tannins.
Target endothelial cells → vascular leakage.
Perirenal oedema.
Acute Tubular Necrosis - oxalate containing plants - cattle + sheep
Calcium oxalates precipitate in BVs or within
renal tubules.
obstruction and epithelial cell necrosis.
Neuromuscular dysfunction → hypocalcaemia
Acute Tubular Necrosis - Ethylene glycol (antifreeze)
Dogs, cats and occasionally pigs.
Readily absorbed from GIT.
Oxidised by hepatic alcohol dehydrogenase to toxic metabolites - glycolic acid and oxalate.
Filtered by the glomeruli.
Direct toxic effect on tubules.
Calcium oxalate crystals precipitate in renal tubular lumens → intrarenal obstruction.
Acute Tubular Necrosis - bacterial toxins
Clostridium perfringens type D → epsilon toxin
Pulpy kidney → acute tubular degeneration and/or necrosis, interstitial oedema + haemorrhage
Diseases of the Interstitium
Interstitial nephritis
renal interstitium - define
fibrovascular stroma that surrounds the nephron
Diseases of the Interstitium - Caused by
Ascending infection → pyelonephritis.
Haematogenous infection of tubules and interstitium → E-coli and Leptospira spp, Canine adenovirus.
Secondary to injury of the vasculature or tubules or glomeruli.
Responses of the interstitium to injury
Oedema.
Haemorrhage.
Inflammation.
Fibrosis.
Diseases of the Interstitium - gross appearance
grey foci on the capsular and cut surface.
Diseases of the Interstitium - Histopathology
Initially oedema, haemorrhage and neutrophilic infiltration. Later lymphocytes and plasma cells. Tubular epithelial degeneration. Vascular compromise. Fibrosis
Diseases of the Interstitium - E-coli septicaemia
E-coli septicaemia:
‘White spotted kidney’
Embolic nephritis or nonsuppurative interstitial nephritis.
Microabscess replaced by lymphocytes, plasma cells and
macrophages.
Diseases of the Interstitium - Equine arteritis virus or PRRS
Multifocal lymphohistiocytic tubulointerstitial nephritis with
interstitial oedema.
Vasculitis - fibrinoid necrosis and lymphohistiocytic infiltrates.
Virus can be found in the endothelium and macrophages
Diseases of the Interstitium - Canine adenovirus infection
viral glomerulitis
Transient immune complex GN.
virus leaves glomeruli - reappears in tubular epithelial cells
Basophilic intranuclear viral inclusions.
Persistence of virus in tubular epithelium for weeks to months.
Viral induced cytolysis → tubular epithelial necrosis → production of chronic lymphoplasmacytic and less commonly histiocytic interstitial nephritis.
Diseases of the Interstitium - Leptospirosis - pathophysiology
Bacterial tubulointerstitial nephritis.
organisms localise in renal interstitial capillaries.
Migrate through vascular endothelium → persist in the interstitial spaces.
Migrate into renal tubular lumina.
Degeneration and necrosis of tubular epithelial cells.
Infiltrate of macrophages, lymphocytes and plasma cells in the interstitium and neutrophils can be present in tubular lumina
Diseases of the Interstitium - Feline infectious peritonitis
Granulomatous necrotising vasculitis.
Interstitial pyogranulomas.
other causes of granulomatous interstitial nephritis - Mycobacteria, Fungi, Parasites.
Responses of the vasculature to injury
Hyperaemia and congestion. Haemorrhage and thrombosis. Infarction. Papillary (medullary crest) necrosis. Embolic nephritis.
causes of haemorrhage in the kidney
Direct trauma.
Coagulopathies.
Septicaemia - erysipelas, streptoccocal infections.
Embolic bacterial diseases → Actinobacillus equuli.
Vasculitis - FIP.
Vascular necrosis → Canine herpesvirus.
DIC.
Disseminated intravascular coagulation
abnormal coagulation → generation of excess thrombin
Diffuse vascular damage → endotoxin induced → exposure of tissue factor → induced activation of extrinsic coagulation to produce thrombin.
Formation of widespread fibrin thrombi in the renal
microcirculation → platelet and coagulation factor consumption → widespread haemorrhages.
Not primary disease but a potential complication of any
condition associated with widespread activation of thrombin.
Results in cortical infarction and ischemic (coagulative) necrosis
Sources of renal emboli
Cardiac mural or valvular thrombi.
Endarteritis in parasitic diseases such equine strongylosis.
Neoplastic cell emboli.
Bacterial or septic emboli → Arcanobacterium pyogenes
in cattle, Erysipelas rhusiopathie in pigs and Staphylococcus aureus in dogs.
Neoplasia of the kidney
<1% of total neoplasms reported.
Usually unilateral.
Primary renal tumours - highly malignant and metastatic disease is common
Epithelial tumours -
Renal adenomas - usually incidental at necropsy.
Epithelial tumours - Renal carcinomas
Large with foci of haemorrhage, necrosis and cystic degeneration, occupy and obliterate one pole of the kidney.
Paraneoplastic condition -polycythaemia - overexpression of erythropoietin
Epithelial tumours - Transitional cell papillomas and
carcinomas
Arise in the renal pelvis and LUT.
Can obstruct urinary outflow.
Can invade into the kidney
Metastatic tumours
Carcinomas and sarcomas arising in other organs can metastasise to the kidneys.
Randomly scattered multiple nodules.
Usually involving both kidneys.
Renal lymphoma - cats and cattle
Diseases of the renal pelvis - Hydronephrosis
Dilation of the renal pelvis d/t obstruction of urine outflow → incr pelvic pressure - atrophy of renal parenchyma.
interstitial vessels collapse + renal blood flow decr - hypoxia and ischemic necrosis - tubular atrophy and interstitial fibrosis.
if bacteria enter hydronephrosis kidney → becomes filled with pus → pyonephrosis
Diseases of the renal pelvis - Hydronephrosis - causes
Congenital malformation. Ureteral/urethral blockage due to urinary calculi. chronic inflammation. Ureteral/urethral neoplasia. Neurogenic functional disorders.
Diseases of the renal pelvis - Hydronephrosis - unilateral
hydronephrosis can be become notable
continual urine production and pooling of urine into the
expanding pelvis.
Diseases of the renal pelvis - Hydronephrosis - Bilateral
uraemia occurs before pelvic enlargement becomes extensive.
Pyelonephritis
Bacterial infection of the pelvis with extension into the renal tubules and concomitant interstitial inflammation.
form of suppurative tubulointerstitial disease.
frequently bilateral and recurrent infections common.
Associated with parturition, service and catheter use
Pyelonephritis - Bacteria involved
Corynebacterium spp, E coli, Staphylococcus
spp, Streptococcus spp, Pseudomonas aeruginosa and
Arcanobacterium pyogenes.
pyelonephritis - Competency of vesicoureteral valve is
compromised
causes incr reflux
when pressure is incr in the urinary bladder - urethral obstruction.
Infl of the bladder wall - cystitis.
Endotoxin from G-ve bacteria - inhibit ureteral peristalsis.
Pyelonephritis - gross
Ureters distended with suppurative exudate.
Exudate in the pelvis and medulla.
May extend into cortex
olar scars.
Infl can extend through the surface of the kidneys - peritonitis.
Pyelonephritis - Histopathology
Transitional epithelium is necrotic and sloughed.
Necrotic debris, fibrin, neutrophils + bacterial adhere to denuded surface and accumulate in tubular lumina.
Interstitial infl, haemorrhage + oedema.
If vasa recta are obstructed - papillary necrosis.
Extend radially into the cortical tubules.
Lymphocytes, plasma cells macrophages and fibrosis.
Primary papillary necrosis
Prolonged treatment or overdose with NSAIDs - damage to medullary interstitial cells.
decr PG synthesis (vasodilator) - decr blood flow - ischemic necrosis of the inner medulla
Secondary papillary necrosis - causes
decr vasa recta blood flow - glomerular amyloidosis or
glomerulosclerosis.
Compression of the vasa recta within the medulla -
interstitial oedema or fibrosis.
Compression of the renal papilla - pelvic calculi, LUT obstruction, pyelonephritis and vesiculoureteral reflux
papilary necrosis - effects on kidney
Sharply delineated coagulative necrosis of the inner medulla.
Eventually sloughs - detached fragment in the pelvis.
Large fragments could obstruct the ureter - hydronephrosis.
formation of calculi
Rarely lead to progressive renal damage + failure.
disease of the LUT - causes
Infection: Neoplasia. Toxins/poisons. Congenital defects. Physical trauma → urolith. Obstruction
defense mechanisms of the LUT
Flushing action of urine minimises risk of ascension of bacteria.
Peristalsis acts to eliminate bacteria with adhesion capabilities.
Inhospitable environment for bacterial growth controlled by urine pH.
Protective urothelial mucus coating.
Innate, humoral and cellular immune responses.
LUT response to injury
Dilation and pressure necrosis caused by obstruction.
Inflammation.
Neoplastic transformation
ectopic ureters
Empty into the urethra, vagina or bladder neck.
Predisposed to obstruction or infection.
Present clinically with urinary continence.
patent urachus
Foals.
Foetal urachus fails to close → direct channel between the bladder and the umbilicus.
Underlying omphalitis or congenital urethral obstruction.
↑ Bladder pressure → due to obstruction → forces urine out into the urachus.
Dribble urine from umbilicus.
acquired causes of obstruction of the LUT
Calculi. Neoplasia. Trauma and inflammation. Circumferential fibrosis. Bladder paralysis. Vaginal and/or uterine prolapse. Feline urologic syndrome - fine struvite crystals in a mucoid protein matrix fill the urethra
Consequences of obstruction of LUT
Distended/ruptured bladder. Transmural ecchymotic haemorrhages. Mucosal ulceration and haemorrhages. peritonitis. Infl
acute cystitis - clinical signs
Dysuria, stranguria and haematuria
acute cystitis - causes
Bacterial infection most common cause.
Uropathogenic E coli in many spp, Corynebacterium renale in cattle and Eubacterium suis in pigs.
Hydrolysis of urea by urease producing bacteria C renale and E suis in pigs - release excessive ammonia damage mucosa & urine pH
acute cystitis - affect of LUT
Denuded oedematous mucosa, adherent neutrophils, bacterial colonies, hyperaemia and haemorrhage
acute cystitis - predisposing factors
Urinary stasis. Infrequent urination Calculi. Catheterisation. Prolonged antibiotic use
Chronic Cystitis - difuse
Thickened mucosa infiltrated with mononuclear infl cells
Submucosal fibrosis.
Hypertrophy of the muscularis.
Chronic Cystitis - follicular
Multiple small red nodules on the mucosal surface.
Hyperplastic lymphoid cells surrounded by hyperaemia and haemorrhage.
Associated with uroliths
Chronic Cystitis - polypoid
Multiple masses of proliferative nodules of connective tissue (polyps).
Lymphocytes and neutrophils
Emphysematous cystitis
Glycosuria enhances bacterial growth.
Glucose split by bacteria - E coli, Clostridium perfringens
release of CO2 into the bladder lumen.
Absorption of gas into the bladder lymphatics - emphysema
Toxic cystitis
Chronic ingestion of bracken fern - enzootic haematuria -
haemorrhage, chronic cystitis or bladder neoplasia.
Active metabolites of cyclophosphamide used to treat neoplasia and IMD
epithelial tumours
Transitional cell papillomas or carcinomas
SCC & adenocarcinomas can arise from transitional epithelium
Metastasis regional lymph nodes, lungs and kidney
Mesenchymal tumours:
Leiomyomas
Fibromas from the lamina propria.
Lymphoma.
Rhabdomyosarcomas
Developmental Disorders - Renal aplasia
failure of one or both kidneys to develop.
Developmental Disorders - Hypoplasia
incomplete development of one or both kidneys
fewer than normal nephrons.
Developmental Disorders - Ectopic kidneys
pelvic canal or inguinal position
histological structure and function usually normal but malposition of the ureters predisposes then to
obstruction - secondary hydronephrosis.
Developmental Disorders - Fused kidneys
fusion of cranial or caudal poles
horseshoe shape
structurally and functionally normal.
Developmental Disorders - Dysplasia
abnormal differentiation in one or both kidneys
Developmental Disorders - Progressive juvenile
nephropathy
Severe bilateral renal fibrosis.
Shrunken pale kidneys with a pitted surface.
Foetal glomeruli, interstitial infl, fibrosis and tubular dilation
