Pathology of the Urinary Tract 1 Flashcards
Multipyramidal (Multilobar) kidneys are present in which species?
pigs, cattle
What animal species has external lobulations of the kidney?
Cattle
What species have unipyramidal (unilobar) kidneys?
Cats, dogs, small ruminants, horses
What is unique about equine kidneys?
- mucous glands in the medulla
- mucus & crystals normally present in renal pelvis
What is unique about mature cat kidneys?
cortex is often yellow due to large lipid content of tubular epithelial cells
kidneys autolyze quickly after…
death
Autolysed tissues make it so it is not possible to detect…
ACUTE tubular necrosis
sampling of ocular fluid from the anterior chamber for urea lvls w/i 24 hr of death indicates…
acute renal failure
The interlobular artery extends into the cortex forming glomerular arterioles where…
high pressure favors filtration
Efferent glomerular arterioles close to subcapsular region create peritubular capillary network where…
low pressure favours reabsorption
Why is the medulla especially sensitive to ischaemia?
Due to relative avascularity & low HCT in the medullary capillaries
How much cardiac output is received in the kidneys?
up to 25%
How much oxygen content do the kidneys receive?
about 10% of the whole body
Why do kidneys receive so much oxygen?
Needed for resorption of essential solutes predominantly cortical function
Kidneys self-regulate the balance of…, ensuring stable…
BP
GFR
Renal artery & its branches are…
end-arteries so goes into cortex then to glomeruli for urinary filtration –> interstitium –> venous flow
Medulla receives…
very little blood flow (primarily for reabsorption)
Glomerular arterioles have high pressure that favours…
filtration
Efferent arterioles favor low pressure which favours
reabsorption
Each nephron functions on an…
all or none basis
Components of a nephron
- Glomerulus
- Bowman’s Capsule
- Proximal Convoluting Tubule
- Loop of Henle
- Distal Convoluting Tubule
if the glomerulus is gone, then the blood supply is gone, meaning there is…
a decrease in urine production
In progressive renal disease, remaining nephrons respond by…
hyperplasia & hypertrophy causing an increase in glomerular filtration & tubular function
Damage to tubule but basement membrane is intact means…
regeneration can occur
What happens when a nephron is defective?
Function is impaired causing essential substances wasted in urine
uriniferous tubule consists of…
nephron & collecting duct
Macula densa is used for…
sodium concentration & BP
why does the glomerulus need high BP?
for filtration purposes
Renal corpuscle consists of…
glomerulus & Bowman’s capsule
Glomerulus produces ultrafiltrate as a result of…
difference btw higher systemic hydrostatic BP & lower hydrostatic pressure in tubules
What plasma proteins are excluded from filtration in the glomerulus?
Albumin & higher molecular weight plasma proteins
What are the 3 main features of the proximal convoluted tubules?
- microvilli w/ brush border
- tight jxns
- lots of mitochondria
What are key features of the distal convoluted tubule & collecting ducts?
- Principal cells - receptors for ADH & aldosterone
- Intercalated cells - role in blood pH homeostasis
- Absorption
- Tight Jxns
The interstitium consists of…
blood vessels, CT
The interstitium expands in disease such as
oedema in acute dz or fibrosis in chronic dz
Selective reabsorption occurs in
specialised tubular epithelial cells
The cells of proximal convoluted tubule are prone to…
ischaemia
Loop of Henle leads to…
- hypotonic filtrate produced via countercurrent exchange
- close association w/ peritubular capillary network
- Na & K ATPase pumps absorb Na & Cl ions
When does the interstitium become abnormal?
Oedema
Cellular infiltration
Amyloid depositions
Fibrosis
What are the basic functions of the kidneys?
- Excretion of waste products
- control of blood volume
- blood pressure
- body fluid pH
- body fluid isotonicity
- Regulation of acid-base balance
- endocrine functions
What triggers the renin-angiotensin system?
Reduced blood supply at juxtaglomerular apparatus
Angiotensin II
- causes vasoconstriction
- induces aldosterone release in adrenal gland –> reduces excretion of NaCl
- Activates ADH in the hypothalamus –> fluid retention
What is the outcome of Renin-Angiotensin System?
Increased BP, salt & water retention
The Renin-Angiotensin system…
maintains BP
Regulates Na Balance
What are the main renal hormones?
EPO
Vit D Metabolism
Hypothalamus & ADH
Fxnl characteristics of kidney
- large amts of primary urine produced, most reabsorbed
- enormous reserve capacity (70% lost before clin signs)
- Regeneration of renal tissue
- glomerular malfunction (causes tubular & interstitial malfunction)
- tubular & interstitial malfunction (causes glomerular malfunction)
What are the portals of entry of injurious stimul & agents?
- Ascension from lower UT
- Haematogenous (infarction, embolic, glomerular tufts, interstitial vessels)
- metabolic (toxic or metabolic substances secreted into filtrate)
What are the kidney defence mechanisms?
- barrier system: glomerular & tubular basement membranes
- monocyte-macrophage system: glomerular mesangium & interstitium
- immune system: innate, humoral, cellular
How does the glomeruli response to injury?
- cellular proliferation
- leukocytic infiltration
- thickening of basement membrane
- hyalinization
- sclerosis
How do the renal tubules respond to injury?
- necrosis, esp of lining of prox tubules
- basement membrane thickening
- cell regeneration if basement membrane intact
- compensatory hypertrophy
How does the renal interstitium respond to injury?
- oedema, haemorrhage, inflammation
- fibrosis
How do the blood vessels of the kidney respond to injury?
- arteritis
- arteriosclerosis
- thrombosis
How does the renal medulla respond to injury?
- accumulation of protein casts
- papilla (inflammation pyelonephritis, amyloid, necrosis)
What are the essential requirements for normal renal fxn that can go wrong and lead to renal failure?
- Adeq perfusion w/ blood (incl BP)
- Adeq fxnl renal rissue
- Normal elim of urine thru UT
What is the index of failure for renal fxn?
- amt of urea retained
Azotaemia is a biochemical abnormality that consists of what parameters?
- increased urea
- increased creatinine
- w/ no clin manifestation of renal dz
Uraemia is a clinical syndrome of renal failure due to…
biochemical disturbances, often due to extra-renal multisystemic lesions
What are the 4 steps of renal insufficiency to renal failure?
- Diminished renal reserve (GFR >50%) -> asymptomatic
- Renal insufficiency (GFR 20-50% of normal) -> azotaemia & polyuria
- Renal failure (GFR 20-25% of normal) -> uraemia w// GI, CV, resp, skeletal complications
- End-stage renal dz (<5% normal) -> terminal stages of uraemia
What is unable to be regulated in kidney failure?
- fluid volume (leads to dehydration)
- Electrolytes (PO4, Ca, Na, K)
- Acid-base balance (metabolic acidosis)
- Metabolic waste excretion
- Endocrine fxns (secondary hyperparathyroidism, non-regn anaemia)
- hypertension
- non-specific effects of uraemic toxins
Failure of Ca to regulate renal failure looks like…
- increased hypercalcaemic nephropathy
- decreased tetany
- osteodystrophy
Failure of Na regulation due to renal failure looks like…
- increased oedema
- decreased dehydration
Failure to regulate K in renal failure looks like…
- increased cardiotoxicity
- decreased muscle weakness
Metabolic acidosis due to renal failure looks like…
- decreased production of ammonia in distal & collecting tubules
- increased retention of H+
- impaired resorption of HCO3-
What are the causes of acute prerenal renal failure?
- sudden & severe BP drop (shock/ischaemia) -OR- interruption of blood flow to kidneys from severe injury or illness
Due to:
* Decreased CO: CHF, arrhythmia, cardiac tamponade
* Shock: systemic vasodilation, anaphylaxis, sepsis
* Hypovolaemia: dehydration, V/D, burns, blood loss
* Vascular ischaemia/obstruction: toxins, thrombi, vasculitis, bacterial emboli
What are the causes of acute intrarenal failure?
- Sudden compromised kidney fxn, direct damage to kidneys by inflammation, toxins, drugs, infection, or reduced blood supply
Due to:
* nephrotoxins & drugs
* infectious agents
* vascular obstruction/ischaemia
* immune-mediated
* tumours
What are the causes of post-renal renal failure?
- sudden obstruction of urine flow (obstruction of ureter by urolithiasis, congenital, injury, bladder tumour, nephrolithiasis)
Acute renal failure can be…
reversible
Clinical signs of renal failure
- rapid onset of oliguria or anuria
- azotaemia
- disturbance in electrolyte balance
- accumulation of metabolic waste
- extra-renal lesions (rare) due to severity of uraemic lesions (stomatitis, gastritis, enteritis, vasculitis –> fibrinoid necrosis of vasc wall (often lung) –> increased permeability –> severe pulm oedema)
Animals die of acute renal failure b/c:
- metabolic acidosis
- hyperkalaemia –> cardiotoxicity
- +/- severe pulm oedema
Chronic renal failure is the end-result of …
Chronic renal dz’s
Chronic renal failure is usually
irreversible
What characterises chronic renal failure?
- prolonged duration & signs of uraemia which are progressive
- death imminent
What are the clinical effects of chronic renal failure?
- D/V/anorexia
- altered Ca/P metabolism
- potential secondary renal PTH
- non-regen anaemia of EPO
- heart (angiotensin-induced hypertension leading to L ventricular hypertrophy; mineralisation of atria; myocardial degeneration; vasculitis; fibrinous pericarditis)
- NS: lethargy, drowsiness, NM twitches, convulsions
- Lung: alveolar wall mineralisation, pulm oedema
- Metabolic acidosis: cachexia, oedema
Non-renal lesions of uraemia
- dehydration
- oedema
- pulmonary oedema
- ulcerative stomatitis, glossitis
- ulcerative, haemorrhagic gastritis
- ulcerative, haemorrhagic enteritis
- fibrinous pericarditis, hydropericardium
- atrial/aortic lesions, ulcerations
- myocardial degeneration
- congestive heart failure, L ventricle hypertrophy
- Vascular lesions
- anaemia, nonregenerative
- mineralisation of soft tissue/stomach
- fibrous osteodystrophy
- secondary hyperparathyroidism
- uraemic encephalopathies
- cachexia
What is the pathomechanism of dehydration causing uraemia?
- PU, V, D
What is the pathomechanism of oedema causing uraemia?
- proteinuria
- Hypoalbuminaemia
- leads to increased glomerular permeability nephrotic syndrome
What is the pathomechanism of pulmonary oedema leading to uraemia?
- vascular damage, increased permeability
What is the pathomechanism of ulcerative stomatitis, glossitis leading to uraemia?
- vascular damage
- ammonia
- ammonia production by bacteria from urea in saliva
What is the pathomechanism of ulcerative, haemorrhagic gastritis leading to uraemia?
- ammonia
- vascular damage
- initially non-inflammatory
- may get infected
What is the pathomechanism of ulcerative, haemorrhagic enteritis leading to uraemia?
- ammonia
- vascular damage
- colitis, oedema in stomach & prox SI
What is the pathomechanism of fibrinous pericarditis, hydropericardium leading to uraemia?
- vascular damage
What is the pathomechanism of atrial/aortic lesions, ulcerations leading to uraemia?
- endothelial/subendothelial damage
What is the pathomechanism of myocardial degeneration leading to uraemia?
- vascular damage
- high K lvls
What is the pathomechanism of CHF, L Ventricle hypertrophy leading to uraemia?
- hypertension, RAAS
What are the pathomechanisms of vascular lesions that lead to uraemia?
- endothelial damage
- secondary thrombosis
- infarction in variety of tissues
What are the pathomechanisms of nonregenerative anaemia leading to uraemia?
- EPO deficiency
What is the pathomechanism of mineralisation of soft tissue/stomach leading to uraemia?
- altered Ca-P metabolism
What is the pathomechanism of fibrous osteodystrophy leading to uraemia?
- altered Ca-P metabolism
- increased syntehsis of PTH
What is the pathomechanism of secondary hyperparathyroidism leading to uraemia?
- altered Ca-P metablism
What is the pathomechanism of uremic encephalopathies leading to uraemia?
- metablic acidosis
- toxic waste products
What pathomechanism of cachexia causes uraemia?
- anorexia
- v/d
What is nephrotic syndrome?
Protein-losing nephropathy
Nephrotic syndrome has damaged…
glomeruli in the presence of normally fxning tubules
What are signs of nephrotic syndrome?
- proteinuria +++
- hypoproteinaemia
- generalised oedema
- hypercholesteraemia/hyperlipidaemia
Clinical syndrome of nephrotic syndrome is characterised by…
- hypoalbuminaemia
- generalised oedema
- hypercholesterolaemia
Proteinuria in absence of UT inflammation is indicative of
glomerular damage
Oedema is the result of…
decreased plasma colloid osmotic pressure, stimulation of RAAS, and release of ADH in response to hypovolaemia
What is the hepatic response to hypoproteinaemia?
- generalised increase in production of proteins incl lipoproteins
- leads to hyperlipoproteinaemia & hypercholesterolaemia
Dependent oedema
Hypoalbuminaemia –> plasma colloid osmotic pressure decreases –> interstitial fluid increases –> circulating vol decreases –> angiotensin activated (ADH release), Na retention increases –> dependent oedema increases
dependent oedema is often seen in…
vental abd & legs due to gravity
Renal aplasia
What is it? Predisposed breeds, assoc’d w/ ?
- absence of kidney/renal tissue (bilateral = incompatible w/ life, unilateral = remaining kidney compensatory hyperplasia and increased vulnerability)
- Predisposed: beagle, doberman, shetland sheepdog
- Assoc’d w/: ureter aplasia, absent vas deferens/epididymis/uterine horns
Renal Hypoplasia
What is it? species affected
- kidney abnormally small but morphologically normal
- species: cats
- fxnl capacity lower to start w/ b/c one is smaller
Renal Ectopia
What is it? Species affected, Predisposed to:
- kidneys misplaced in pelvic cavity or inguinal region
- unilateral in pigs/cats/dogs
- Predisposed to: ureteral obstruction, hydronephrosis, pyelonephritis
Renal Fusion
Significance, appearance
- Appearance: horseshoe kidney
- Significance: no clinical pathological significance
Renal cysts
What is it? species affected? acquired how? Mechanism?
- Cysts variable sized fluid-filled spaces lined by flattened epithelium anywhere in nephron
- Species: All
- Acquired by: chronic interstitial lesion, steroid txt, dialysis, assoc’d w/ renal dysplasia, chronic renal dz
- Mechanism: obstruction of nephron, saccular dilation of tubules due to defective basement membrane, focal tubular epithelial hyperplasia
Polycystic kidney dz
Species/breeds; associations, commonly leads to
- species/breeds: cats (persians), dogs (Cairn terriers, WHWT), lambs, pigs, calves, foals
- Associations: cystic bile ducts, pancreatic cysts, bile duct proliferation
- Commonly leads to: stillbirth, neonatal death, chronic renal failure in 1st few wks of life
Familial Renal Dz’s in dogs includes Progressive Juvenile Nephropathy. What is it?
- aka Renal dysplasia
- non-inflammatory, degenerative, or dvlpmtl chronic renal dz, nephron impacted of obscure pathogenesis in young animals
- inbred lines of animals (mostly dogs)
- young dogs: 4 mos to 5 yrs
- progressive renal failure
Renal dysplasia
What is it? Causes? Consequences?
- Altered structural organisation that results from abnromal renal dvlpmt/differentiation
- causes: familial renal dz in dogs or inherited renal dz in Suffolk shep, Japanese black cattle; foetal infection by teratogenic virus; in utero ureteral obstruction; hypovitaminosis A in piglets; anything that disrupts organogenesis
- Consequences: diffuse & bilateral –> fxnl overloading of renal excretory capacity w/ time causes uraemia in 1st yr or 2 in life; any superimposed inflammation will hasten onset & dvlpmt of clin syndrome; ureteral anomalies concomitant, dysplastic kidneys abnormally susc to pyelonephritis
What are specific tubular dysfxns of multiple transport defects?
- Fanconi syndrome: Basenjis
- Poor reabsorption of glucose/PO4/Na/K/Uric Acid/ AA’s from prox tubules –> PU, progressive renal failure
What are specific tubular dysfxn due to single transport defects?
- glucose –> Norwegian Elkhounds
- Cystine –> some male dogs
- No morphological changes
Nephrogenic Diabetes insipidus
- dogs, foals
- Lack of responsiveness of cells of distal tubules & collecting ducts to ADH
- congenital or acq’d tubulointerstitial dz
