Renal Physiology & The Urinary Tract Flashcards
1
Q
What adult structures are formed by the urachal structures?
A
Urachal remnant: middle ligament of the bladder
Umbilical arteries: round ligaments of the free border of the paired lateral ligaments of the bladder
2
Q
Where in the urethra are the various ducts located in males?
A
- Colliculis seminalis (common openings of the ductus deferens and ducts of the seminal vesicles) is a dorsal papilla immediately caudal to the urethral opening.
- Prostatic ducts are two small papilla lateral to the colliculus seminalis.
- Bulbourethral glands open in paired dorsal lines 2-3c, caudad to the colliculis seminalis.
- Lateral urethral glands are smaller ducts at the same level as the bulbourethral glands, but they are laterally located.
3
Q
What are the two types of nephrons?
A
- The superficial or cortical nephrons with short loops of Henle.
- The juxtamedullary nephrons with long loops of Henle.
4
Q
List the effects of stimulation of the renal nerves.
A
- Predominantly sympathetic
- Control of renal vascular resistance (vasoconstriction or dilation)
- Increased proximal tubular sodium reabsorption and renin release by activation of a1adrenoceptors (with low frequency stimulation of the nerve)
- Increased perfusion of the outer renal medulla (dopamine D1 receptors) - presence of these receptors is the basis for use of dopamine and DA-1 receptor agonist fenoldopam to improve renal blood flow in acute renal failure.
5
Q
Where does the sympathetic and parasympathetic innervation to the bladder arise?
A
Sympathetic: hypogastric nerve with pre-ganglionic fibres from spinal segments L1-L4 to synapse in the caudal mesenteric ganglion. Post-ganglionic fibres supples the bladder (B2adrenergic receptors) and proximal urethra (primariily A1 and some A2adrenergic receptors).
Parasympathetic: sacral segments of the spinal cords with neurons joining to form the pelvic nerve.
Somatic innervation of the lower urinary tract is primarily to the striated muscle of the external urethral spincter via a branch of the pudendal nerve from S1-S2.
6
Q
What other abnormalities commonly accompany congenital defects of the kidney such as renal agenesis or dysplasia?
A
- Ureteral dysgenesis or ectopic ureters
- Cryptorchidism/urogenital defects
7
Q
What is the most common site of renal cysts?
A
Most often in the cortex but can occur from any portion of the nephron.
8
Q
What are the treatment options and considerations for unilateral renal vascular anomalies?
A
- Unilateral nephrectomy
- Selective renal embolisation
- Conservative treatment (only if bleeding is minor and not associated with anaemia)
Treatment is only likely to be effective if the defect is not associated with azotaemia.
9
Q
Ectopic ureters are more commonly reported in females than males - what could influence this finding?
A
The longer length of the male urethra makes retrograde urine flow more likely in males, hence urinary incontinence doesn’t occur. Likewise urinary incontinence is more easily identified in females than males.
10
Q
What are the diagnostic methods for ectopic ureteral location?
A
IV dyes (sodium fluorescein, indigo carmine, azosulfamide etc may discolour the urine to help with endoscopic localisation.
Ultrasound guided pyelography with contrast agent may be useful.
Contrast enhanced CT in small patients.
11
Q
What surgical options are available for ectopic ureter/ureters and what may need to be measured first?
A
- Ureterocystotomy (unilateral or bilateral) - prior to this, measure the intra-vesicular pressure response to progressive distention until voidance to ensure competency of the urethral sphincter prior to reimplantation.
- Unilateral nephrectomy - ensure the other kidney is functional and the ureter is patent and in a normal position.
12
Q
What factors would lead you to suspect a ureteral tear rather than a bladder or urachal tear in a case of uroperitoneum?
A
- Delayed onset of clinical signs/slower progression
- Mild protrusion of the vagina in fillies if the peritoneum is intact
- Continued development of peritoneal effusion and ongoing/refractory electrolyte derangements despite placement of a urinary catheter/bladder drainage
13
Q
What therapies are available for an enlarged bladder in a sick, recumbent neonate?
A
- Bethanecol (cholinergic drug) to improve detrusor function (no reports of true efficacy with this medication).
- Acepromezine (A-adrenergic blocker) to decrease urethral sphincter tone (no reports of true efficacy with this medication).
- Indwelling urinary catheter +/- use of phenazopyridine as a local analgesic to reduce lower urinary tract discomfort and spasm and allow relaxation of the bladder sphincters.
14
Q
What non-renal factors may influence urea and creatinine concentrations in blood?
A
Urea: Protein catabolism with fasting/weight loss (except in ponies), protein supplementation in the diet, prolonged exercise (secondary to protein catabolism; reduced renal blood flow may also influence).
Creatinine: Placental insufficiency in newborns, fasting, rhabdomyolysis or muscle wasting caused by disease or exercise.
15
Q
What is the role of vasopressin/ADH?
A
- Principle controller of renal water reabsorption.
- Vasopressin acts on V2 receptors on the basolateral membrane of collecting duct epithelial cells, leading to insertion of water channels in the apical membrane.
- Channels increase the water permeability and lead to increased water reabsorption.
- V2 receptor activation can be antagonised by activation of adjacent A2 adrenoceptors and PGE2 effects - the A2 effects may be responsiblel for diuresis associated with their administration.
16
Q
What is the proposed mechanism for why horses don’t always drink when they become dehydrated due to prolonged exercise or colitis?
A
Loss of water is in proportion to loss of osmoles (in sweat and diarrhoea) hence plasma osmolality doesn’t increase and osmotic thirst stimulus is not produced.
17
Q
What percentage of cardiac output do the kidneys receive at rest?
A
15-20%
18
Q
Why is the renal medulla typically hypoxic?
A
Renal blood flow is delivered preferentially to the cortex; medullary flow is derived largely from the vasa recta that arise from the efferent arterioles of juxtamedullary glomeruli (<20% renal blood flow).
19
Q
What are the protective mechanisms to preserve medullary blood flow and oxygenation and how do NSAIDs influence these?
A
During renal hypoperfusion there is a preferential reduction in cortical blood flow and redistribution of renal blood flow to the corticomedullary region. In addition production of PGE2 and PGI2 as well as nitric oxide cause vasodilation. Administration of NSAIDs in patients with poor renal perfusion exacerbates hypoxic injury as it prevents these protective mechanisms.
20
Q
What is the rationale for administration of dopamine infusions in acute renal failure?
A
Dopamine receptors are located on most renal arteries so blood flow increases in the renal cortex and medulla in response to activation of these receptors, hence they increase renal blood flow and urine output in normal horses and may be of benefit in horses with ARF.
21
Q
What is the glomerular filtration rate (GFR) of horses?
A
1.6-2mL/kg/min or filtration of the total plasma volume 60-70 times per day.
22
Q
Why does glomerular filtration rate (GFR) reduce less so than renal blood flow with renal vasoconstriction?
A
Greater vasoconstrictive effects of angiotensin II on efferent arterioles compared with afferent arterioles.
23
Q
Which segments of the nephron are most susceptible to hypoxic injury with reduced renal perfusion and why?
A
Proximal tubule: these cells have a high metabolic rate so despite being predominantly in the relative more highly perfused cortex you get a relative hypoxia around these cells due to ongoing metabolic activity, so the proximal tubule is highly susceptible to injury with reduced cortical flow.
Medullary thick ascending loop: As the renal medulla only receives a relatively small fraction of total renal flow it is normally in a relatively hypoxic environment so any degree of renal hypoperfusion leads to exacerbation of medullary hypoxia, particularly in the inner stripe which has a high metabolic activity (primarily of the epithelial cells lining the medullary thick ascending loop of Henle). Tx with CRI of furosemide may help reduce the metabolic rate of these cells and may protect against hypoxic injury.
24
Q
What are the main causes of hyponatraemia?
A
Ruptured bladder
Diarrhoea
Defective water excretion (pre-renal eg hypovolaemia)
Oliguric renal failure after reduction of GFR
Loop diuretics (blockade of the apical Na/K/2Cl cotransporter)
Inappropriate vasopressin/ADH secretion (not documented in equids)
25
What is the biphasic effect of efferent arteriolar constriction on GFR?
At moderate levels of constriction there is a slight increase in GFR due to increased resistance to outflow from the glomerular capillaries, raising hydrostatic pressure.
A more marked vasoconstriction reduces renal blood flow, hence the filtration fraction and glomerular colloid osmotic pressure increases beyond the glomerular capillary hydrostatic pressure and decreases the force for filtration.
26
What are the effects of angiotensin II on GFR, water and sodium dynamics?
Angiotensin II preferentially constricts effeerent arterioles thereby increasing glomerular hydrostatic pressure (its usually released in response to decreased arterial pressure or hypovolaemia) therefore protecting against reduced GFR. So angiotensin II helps maintain normal GFR and excretion of wastes while also increasing tubular reabsorption of sodium and water to help restore blood volume and pressure.
27
What do the macula densa cells sense and what effects does this have?
Macula densa cells detect changes in volume delivery to the distal tubule. Decreased GFR causes reduced flow rate in the loop of henle and increased reabsorption of Na and Cl in the ascending loop, hence decreasing the concentration of NaCl at the macula densa cells which iniatiates a signal from these cells with 2 effects:
1. decreases resistance to blood flow in the afferent arterioles, raising glomerular hydrostatic pressure, returning GFR toward normal; 2. increases renin release from juxtaglomerular cells of the afferent and efferent arterioles. Renin is an enzyme that increases formation of angiotensin I which is converted to angiotensin II which constricts efferent arterioles, hence increasing glomerular hydrostatic pressure and returning GFR toward normal.
28
How does the Na/K ATPase pump facilitate sodium reabsorption in the tubule?
Pumping of sodium out of the cell to the interstitium and potassium into the cell from the interstitium creates a negative charge of ~-70mv within the cell. This then favours passive diffusion of Na across the luminal membrane of the cell from the tubule because of the concentration gradient (low intracellular concentration of Na) and because the negative charge intracellularly attracts the positively charged Na. This occurs in most parts of the tubule.
29
In addition to the Na/K ATPase pump, what other mechanisms are there for Na reabsorption?
In the proximal tubule the extensive brush border increases the surface area for reabsorption by ~20fold.
Sodium carrier proteins bind Na on the luminal side and release them intracellularly (facilitated transport) and may also provide important secondary active transport for other substances eg glucose and amino acids.
Na, H2O other substances are also reabsorbed from the intesrtitial fluid into the peritubular capillaries by ultrafiltration which is passive, driven by the hydrostatic and colloid osmotic pressure gradients.
Secondary active transport one substance moves down its concentration gradient (eg Na) and the energy released by this process is used to drive another substance (such as glucose) against its electrochemical gradient.
30
How does water move across the tubular epithelium of the nephron?
As solutes move to the interstitium (either passively or by active transport) they create a concentration gradient that enables osmotic movement of water to the interstitium. The proximal tubule is highly permeable and water reabsorption occurs rapidly here (and brings some solutes with it via solvent drag). In the more distal tubule (loop of Henle through to the collecting tubule) the tight junctions are less permeable to water and solutes and the epithelial cells have reduced membrane surface area, which reduces movement of water. However ADH increases permeability in the distal and collecting tubules. Water permeability remains low in the ascending loop of Henle, but in the presence of ADH it can be high in the distal tubules, collecting tubules and collecting ducts (controlled essentially by ADH).
31
How is chloride reabsorbed in the tubule?
The transport of Na out of the tubule leaves the tubule negatively charged compared to the interstitial fluid which causes passive diffusion of Cl through the paracellular pathway.
In addition as water is reabsorbed the Cl in the tubular lumen becomes concentrated, causing transport down the concentration gradient. Hence active reabsorption of Na is closely coupled to passive reabsroption of Cl.
Cl can also be reabsorbed by secondary active transport, most commonly with Na across the luminal membrane.
32
How does osmolarity and concentration of Na remain fairly constant in the proximal tubule despite reabsorption?
The amount of Na decreases markedly but the concentration remains the same due to marked water reabsorption in this segment.
33
Describe the permeability along the different segments of the loop of Henle.
Thin descending limb: highly permeable to water and moderately permeable to most solutes, including urea and sodium. Allows simple diffuseion of substances through its wall and almost all of the ~20% filtered water that is reabsorbed in the loop of Henle occurs in his segment.
Thin ascending limb: virtually impermeable to water, and minimal reabsorption of solutes.
Thick ascending limb: thick cells with high metabolic rate, capable active reabsorption of Na, Cl and K. Most of the ~25% filtered load of Na, Cl and K that are reabsorbed in the loop of Henle, are reabsorbed in this portion. Ca, bicarbonate and Mg are also reabsorbed in this segment. Movement of Na across the luminal membrane is mediated primarily by Na/K/2Cl co transporter and this is the site of action of frusemide (loop diuretics). Also significant paracellular reabsorption of Mg, Ca, Na and K due to the slight positive charge of the tubular lumen relative to the interstitial fluid. There is a slight back leak of K into the lumen which creates the positive charge that forces diffusion of Mg and Ca from the lumen. There is also a Na/H counter transport mechanism that mediates Na reabsorption and H secretion in this segment. Virtually impermeable to water, hence the fluid becomes dilute as it flows towards the distal tubule.
34
Describe the function & permeability of the distal tubule & collecting ducts.
The first portion provides part of the juxtaglomerular complex giving feedback control of GFR and blood flow.
The convoluted part has similar characteristics of the TAL (reabsorbs most of the ions incl Na, K and Cl; relatively impermeable to water and urea). Na/Cl cotransporter moves NaCl out of the tubular lumen (thiazide diuretics inhibit this transport system)
The second half of the distal tubule and cortical collecting tubule are composed of principal cells and intercalated cells. Principal cells reabsorb Na and H2O and secrete K into the lumen (facilitated by high intracellular K and low intracellular Na concentrations due to Na/K ATPase pumps on the basolateral membrane). The intercalated cells reabsorb K and secrete H into the lumen.
Collecting ducts: Final site for processing urine. Permeability of the medullary collecting duct to water is controlled by the level of ADH. This segment is permeable to urea so some urea is reabsorbed into the medullary interstitium, helping to raise the osmolality in this region. The medullary collecting duct is capable of secreting hydrogen ions against a large concentration gradient as occurs in the cortical collecting duct, hence these regions play an important role in regulating acid-base.
35
How do Na-channel blockers and aldosterone antagonists decrease urinary excretion of K and act as K sparing diuretics?
The principle cells of the distal tubule and cortical tubule have Na/K ATPase pumps on the basolateral membrane that maintains the high K/low Na intracellular environment that facilitates Na reabsorption and K secretion in this segment. These diuretics inhibit entry of Na into the Na channels of the luminal membranes, thereby reducing the amount of Na that can be subsequently exchanged for K via the Na/K ATPase pumps and ultimately the amount of K available for secretion into the tubular fluid.
36
How is BUN : Cr used to differentiate different times of azotaemia (ie pre-renal and post-renal from renal causes and acute from chronic kidney disease)?
Pre-renal and post-renal azotaemia: BUN : Cr should be higher due to increased reabsorption of urea with low tubule flow rates in pre-renal and preferential diffuseion of urea across peritoneal membranes in post-renal cases such as uroperitoneum.
Acute renal failure and chronic kidney disease: BUN : Cr will often be less than 10:1.265 for ARF due to a proportionately higher increase in Cr compared with BUN. In contrast, with CKD the BUN : Cr often exceeds 10:1. The explanation for why is not clear but one theory is that urea is a nonpolar molecule that diffuses freely into all body fluids whereas Cr is a charged molecule that likely takes longer to diffuse out of extracellular fluid hence a sudden decrease in renal perfusion leads to a greater increase in Cr than in BUN.
37
What measurements can help differentiate pre-renal failure from intrinsic renal failure?
- Maintenance of adequate concentrating ability and osmolality (USG >1.020, osmolality >500mOsm/kg)
- Urine : serum creatinine ratios >50:1 (concentrated urine) and fraction Na clearance <1% (indicating adequate tubule function) would be expected with pre-renal failure.
- Urine : serum creatinine ratios <37:1 and clearance values >0.8% my be seen with intrinsic renal failure.
Progression from pre-renal failure to intrinsic renal failure is associated with decompensation of the intrarenal responses to hypoperfusion.
38
What degree of increase in peritoneal fluid creatinine relative to serum creatinine concentration do you expect with uroperitoneum?
Two-fold or greater increase in the peritoneal creatinine concentration relative to the serum creatinine concentration.
39
Differentiate Ca and P concentrations in horses with ARF versus CKD
Hypercalcaemia and hypophosphataemia often occurs with CKD (although can also be hyperphosphataemia:
- Osteodystrophy of CKD has been associated with aluminium deposition in skeletal muscle which may inhibit buffering capacity for increases in hypercalcaemia.
- Impaired tubular function in the face of ongoing intestinal absorption of Ca.
Hypocalcaemia and hyperphosphataemia with ARF:
- Resistance to parathyroid hormone
- Down regulation of renal calcitriol (Vit D)
- Damage to tubular epithelial cells may result in reduced absorption of Ca.
40
Differentiate the likely source of pigment with pigmenturia at different stages in urination.
Start or end of urination: lesions of the urethra or accessory sex glands in males.
Throughout urination: myonecrosis or a bladder or kidney lesion.
An exception is blood clots with cystitis which may occasionally be passed more frequently at the end of urination due to sedimentation of the clot with time.
41
Explain paradoxic aciduria.
Instead of reflecting metabolic acidosis, paradoxic aciduria reflects hypochloraemic metabolic alkalosis. After all Cl has been reabsorbed from the glomerular filtrate further Na reabsorption occurs by exchange with K and H ions, hence paradoxic aciduria occurs with concomitant hypokalemia.
42
How do you differentiate between different causes of pigmenturia?
Evaluation of serum for haemolysis and urine sediment for red blood cells to differentiate between haemoglobin and whole red blood cells and perform an ammonium sulphate precipitation test to detect myoglobin.
43
List the causes of bilirubinuria
Intravascular haemolysis, hepatic necrosis and obstructive hepatopathies.
44
What is the significance of identification of casts and crystals on urine sediment examination in equids?
Casts: molds of Tamm-Horsfall glycoprotein and cells that form in the tubules and pass into the bladder. They can be associated with both inflammatory and infectious processes but are rare in normal equine urine. They are also unstable in alkaline urine so may not be detected.
Equine urine is rich in crystals, most of which are calcium carbonate (CaCO3) and to a lesser degree calcium phosphate and calcium oxlatate. These are normal findings.
45
Explain the benefit of measuring urinary enzyme concentrations.
Inflammation or necrosis of tubular epithelial cells can result in elevated urinary activity of lysosomal and brush border enzymes. Determination of the activities of certain urinary enzymes can provide evidence of tubular damage several days before azotaemia develops. Different enzymes are present or more prevalent in certain regions of the nephron and as such assessment of changes in the urinary activity of selected enzymes may assist the clinician in identifying the segment of the nephron suffering the greatest dysfunction or damage. However, it is not considered a routine measure of renal damage and is probably of limited use as a single measure.
46
List the urinary enzymes that may be useful in identifying renal damage and the site to which injury has most likely occurred.
NAG: proximal tubular epithelium
GGT: brush border of proximal tubular epithelium (may be induced by aminoglycosides)
ALP: brush border of proximal tubular epithelium (may be induced by aminoglycosides)
LDH: distal tubular epithelium, proximal tubular epithelium and medullary papillae
In reality the usefulness of these enzymes is questionable, particulary as single measurements, perhaps with the exception of GGT which may precede azotaemia and could therefore be a useful warning of the need to discontinue nephrotoxic medication.
47
Differentiate urinary clearance rate and urinary fractional excretion for measurement of electrolytes.
Urinary clearance rate involves a timed urine collection to determine urine flow in mL/min and measuring the concentration of the desired substance in plasma and urine. Equation is: ClA/ClCr= (Urine[A]/Plasma[A]) x urine flow/(Urine[Cr]/Plasma[Cr]) x urine flow
Fractional excretion is comparing the clearance of a substance with the clearance of creatinine and expressing as a fraction. This avoids the need for timed urinary collection. The equation is: ClA/ClCr= Urine[A]/Plasma[A] x Plasma[Cr]/Urine[Cr] x 100
48
What are the expected outcomes of a water deprivation test and what would indicate the test needs to be stopped or is contraindicated?
Contraindications: Clinical dehydration of azotaemia.
Indications to stop: more than 5% body weight is lost or clinical evidence of dehydration develops.
Expected outcome: concentration of the urine to 1.045 or osmolality >1500mOsm/kg within 24-72hrs.
If polydypsia has been long standing medullary washout may prevent concentration below 1.025. A better result will be achieved after a period of partial water deprivation during which daily water intake is limited to 40mL/kg for several days to enable restoration of the medullary interstitial osmotic gradient.
Central or nephrogenic diabetes insipidus will result in absence of urinary concentration. If you suspect this, monitor them every few hours as significant dehydratin may occur within 6 hours due to lack of concentrating ability.
To differentiate between central and nephrogenic, administer exogenous vasopressin (20U/mL IM) - an increase in USG to 1.020 or above after 60-90min is expected; failure to do so suggests nephrogenic diabetes insipidus.
To identify central diabetes insipidus you would need to measure baseline plasma osmolality and endogenous vasopressin concentration, then administer 1-2mL/kg of 7.5% NaCl (hypertonic). A normal response would be increase in plasma vasopressin concentration and USG. However assays for plasma vasopressin are not available.
49
How is GFR estimated and what is the limitation?
Empty the bladder then do a timed urine collection for 12-24hours including emptying the bladder at the end of the test period. Measure the test substance (usually creatinine or inulin) in the pooled urine as well as plasma creatinine or inulin collected near the midpoint of the urine collection. Calculate as: GFR= (Urine[Cr]/Plasma[Cr]) x urine flow. This can be divided by BW in kg to express GFR in mL/min/kg. Creatinine underestimates GFR due to non-Cr chormagens in serum that artifactually inrease the value in the denominator. Similarly, significant tubular secretion of Cr can be one of the compensatory responses to renal failure. For inulin to be used it has to be administered as an infusion throughout the collection period.
50
What are the three forms of ARF and which are more common?
Oliguric renal failure (more common)
Anuric renal failure (more common)
Non-oliguric renal failure (less common but may be associated with a more rapid recovery of renal function with Tx)
51
What is acute tubular necrosis?
Most commonly recognised intrinsic renal failure (interstitial and primary glomerula disease are recognised occasionally and vascular disease is rarely seen).
Ischaemia, especially when associated with microvascular coagulation that may lead to irreversible cortical necrosis; and nephrotoxins are the most common causes of ATN - aminoglycosides bind in a saturable fashion to the brush border of the proximal tubule; Ca competitively inhibits aminoglycoside binding so may be protective. Can also develop after exposure to pigment, heavy metals like mercury or vitamins D or K3. As part of the pathophysiology GFR is reduced due to increased Na and Cl presented to the macula densa secondary to dysfunction of proximal sodium reabsorption. You are also more likely to see granular casts and develope enzymuria.
52
Describe the pathophysiology of acute renal failure.
Initially with hypovolaemia the systemic response include activation of the autonomic nervous system and renin-angiotensin system and release of ADH. One effect of this is peripheral vasoconstriction. Initially tubular reabsorption of Na and H2O increases. However with more severe hypovolaemia the renal autoregulation responses are overcome and renal blood flow is redistributed to the medulla and GFR declines. The renal circulatory changes further enhance tubule solute reabsorption in the face of decreased GFR. Further reduction in renal blood flow results in a syndrome intermediate between pre-renal and intrinsic renal failure that is characterised by increased output of dilute urine (may be mildly polyuric). As the hypoperfusion persists non-oliguric and then oliguric ARF develop. Administration of NSAIDs exacerbates as it impairs the intrinsic protective vasodilatory mechanism of PGE2 and PGI2 which normally protect against the vasoconstricting effects of angiontensin II. In their absence there is a significant increase in renal vascular resistance. After a while the renal blood flow autoregulation is lost and reversal of vasoconstriction may not improve GFR. GFR may also be compromised by cell swelling secondary to prolonged hypoxia and obstruction with luminal casts/debris - this is a reason why furosemide or mannitol may be beneficial, to increase solute excretion rate. Loss of brush borders and polarity in the proximal tubule cells means the glomerular filtrate is able to cross back into the peritubular circulation hence reducing effective GFR. Loss of reabsorptive capacity triggers tubulo-glomerular feedback and further reduces GFR by lowering renal blood flow after vasoconstriction and a decrease in the glomerular ultrafiltration coefficient.
53
What is the likely mechanism behind development of acute interstitial nephritis?
Most likely caused by delayed cell mediated hypersensitivity or the presence of antitubule basement membrane antibodies. In people it may be corticosteroid responsive. Prognosis is usually grave in horses.
54
List the 6 possible syndromes associated with ARF that may be associated with azotaemia.
1. Pre-renal ARF, 2. Ischaemic ARF, 3. Acute tubular necrosis, 4. Acute interstitial nephritis, 5. Acute glomerulonephritis, 6. Obstructive (post renal) ARF.
55
Describe the treatment of ARF.
Initially reverse the underlying cause and correct fluid and electrolyte imbalances over 6-12hrs.
Physiologic saline or balanced electrolyte solutions are suitable unless hypernatraemic in which case 0.45% NaCl or 2.5% dextrose are recommended. Addition of 50-100g of dextrose/L fluid helps address caloric requirements in anorexic horse. If early in the disease process diuresis should result, in which case continue at twice maintenance until serum Cr decreases dramatically then reduce to maintenance until Cr is normal or the horse is eating & drinking adequately.
If the horse remains oliguric 10-12hrs after Tx, administration of dopamine in 5% dextrose (3-5ug/kg/min) may improve renal blood flow and urine output. Monitor blood pressure due to risk of hypertension and overhydration in oliguric patients. Furosemide may be helpful both for promoting diuresis but also reducing the metabolic rate and O2 demand of the ascending limb tubule cells. Ensure there has been adequate volume replacement before their use otherwise they are contraindicated. Mannitol 20% 0.25-1g/kg given over 15-20min may help combat oliguria by increasing renal blood flow and GFR. Mannitol may induce synthesis of PGE2 which is a vasodilator and release of atrial natriuretic peptide to increase renal blood flow. If hyperkalaemia is present (most common with post-renal obstruction) it usually responds to administration of K free fluids or if refractory, correction of acidosis with NaHCO3 or glucose or both usually helps. In the worst cases insulin may be necessary.
56
What factors determine the prognosis for ARF?
- Duration of ARF before beginning therapy (most important determinant of prognosis)
- Animals that display prolonged oliguria or anuria (12 hours+) despite institution of appropriate therapy carry a poor prognosis.
- Severe ischaemic failure and acute interstitial nephritis carry the worst prognosis.
- Some horses recover but never fully regain the ability to concentrate urine as well as previously.
57
What causes glomerulonephritis?
Deposition of circulating immune complexes along the glomerular basement membrane an din the mesanguim leading to complement activation and leucocyte infiltration and adherence. These lead to release of oxidants and growth factors by macrophages and mesangial cells and platelet aggregation and activation of coagulation factors which leads to endothelial and epithelial cell swelling, formation of microthrombi in glomerular capillaries and mesangial cell proliferation. The GBM proliferates to surround the immune deposits, leading to irregular thickening of the filtration barrier and reduction of the GFR.
58
List the causes of tubulointerstitial disease/chronic interstitial nephritis.
- Secondary to acute tubular necrosis which can occur as a result of ischaemia, endotoxaemia, sepsis or exposure to nephrotoxic compounds
- Severe localised infection or septicaemia such as pleuritis or peritonitis
- Intravascular haemolysis or rhabdomyolysis can lead to acute tubular damage
- Ascending urinary tract infections resulting in pyelonephritis or bilateral obstructive disease caused by ureteroliths or nephroliths
- Immune mechanisms (antitubular basement membrane disease)
59
Differentiate chronic interstitial nephritis from acute tubular and interstitial disease.
The main distinguishing factor is the presence of interstitial fibrosis - chronic interstitial nephritis encompasses all extraglomerular causes of chronic kidney disease. As such you don't get haematoria, proteinuria,
60
What is uremic syndrome?
A multisystemic disorder that develops as a result of the effects of uremic toxins on cell metabolism and function. High levels of BUN have been associated with lethargy, weakness, anorexia, vomiting and bleeding diathesis secondary to platelet dysfunction. Excess urea also can degrade to ammonia, carbonate or cyanate. Cyanate interferes with enzyme activity and structural integrity of cell membranes, hence accumulation of urea is likely responsible for some or all of the signs of uremic syndrome. Products from intestinal bacterial metabolism also can contribute to the clinical signs of uremic syndrome and neurologic disease, including GIT ulceration and PLE secondary to ammonia from increased GIT urea, oral ulceration from urea excretion in saliva. Presumed uremic encephalopathy has been reported in horses with CKD - swollen astrocytes were observed histologically in those examined.
61
What are the clinical signs of CKD?
- Lethargy, weight loss and anorexia.
- Increased nitrogenous wastes in the blood can have a direct appetite suppressive effect.
- With azotaemia, excess urea diffuses across the GIT epithelium and is metabolised to ammonia and CO2. Here it causes ulceration and mild-moderate PLE or soft faeces in severe cases
- Urea is excreted in saliva where it can lead to excessive dental tartar formation, gingivitis and oral ulcers.
- Ventral oedema secondary to several factors including decreased oncotic pressure, increased vascular permeability, increased hydrostatic pressure (secondary to activation of renin-angiotensin system) and the effects of uremic toxins on endothelial cell membranes which alters the vascular permeability.
62
List common aberrations in haematology and clinical chemistry with CKD.
- Mild anaemia (non-regenerative due to deficiency of erythropoietin, as well as potentially reduced erythrocyte lifespan)
- Hypoalbuminaemia
- Hyponatraemia
- Hyperkalaemia
- Hypochloraemia
- Hypercalcaemia
- Hypophosphataemia
- Metabolic acidosis
63
What is the cause for reduced erythrocyte lifespan in horses with CKD?
Excessive nitrogen waste products alter the integrity of erythrocyte membranes and the function of ion channels which regulate erythrocyte volume. The less resilient erythrocytes are more likely to be removed from the circulation by the reticuloendothelial system.
64
What are the common acid base findings in horses with CKD and how do these change with disease progression?
- Acid base balance is usually maintained during the early stages
- Metabolic alkalosis may develop during CKD, and may be associated with paradoxic aciduria
- During the terminal stages of CKD metabolic acidosis develops and may contribute to some of the signs of uremic syndrome and exacerbate electrolyte alterations (eg hyperkalaemia).
65
List contributors to the disease progression of CKD
- Response to reduced functional renal mass is a compensatory increase in filtration and tubular function by the remaining nephrons.
- Hyperfiltration is associated with increased permeability of the GBM and proteinuria as well as activation and proliferation of mesangial and epithelial cells and eventually progression to glomeruloscerosis.
- Increased filtration of protein leads increased proximal tubular protein reabsorption which upregulates vasoactive and inflammatory mediators in tubular and interstitial cells and contributes to injury of the renal interstitium.
- Activation of intrarenal renin-angiotensin system produces glomerular hypertension
66
What dietary considerations are required in cases of CKD?
- Decreasing dietary protein results in reduction in nitrogenous wastes which may reduce the workload of the kidneys.
- Increased protein has been shown to increase activation of the renin-angiotensin system so decreasing protein may be protective but this remains controversial.
- Increased protein results in increased free radicals which are injurious to disease kidneys as their scavenging mechanisms are injured.
- Protein-calorie malnutrition is associated with increased morbidity and mortality in human patients, including protein catabolism.
- Current recommendations are provision of protein and caloric intake at levels that meet or only slightly exceed the predicted requirements; this should result in a neutral nitrogen balance. A palatable diet is critical and feeding small meals more frequently is important.
67
What treatment options are available for horses with CKD?
- Peritoneal dialysis or haemodialysis may be an option in valuable horses or in cases of pyelonephritis where antibiotic treatment may result in resolution of infection and improved renal function
- Palliative care is the mainstay
- IVFT with 0.9% NaCl is less useful in CKD but may be of use in patients that suffer a sudden exacerbation of CKD. Caution is necessary as these patients are at higher risk of developing significant peripheral or pulmonary oedema.
- Supplementation of NaHCO3 may be indicated if levels are consistently less than 20mEq/L (monitor for development of ventral oedema)
- If oedema develops it should be tolerated unless it interferes with ambulation - this is preferable to administration of diuretics which may exacerbate electrolyte wastage, or be ineffective.
- Substitute high Ca and high protein feeds such as alfalfa for feeds such as good quality grass hay and carbohydrates to help control hypercalcaemia and ureamia.
- Target BUN : Cr of 10:1-15:1
- Administration of B vitamins or anabolic steroids for appetite stimulation may be helpful in some horses
- NSAIDs and corticosteroids are NOT RECOMMENDED as the benefits of reduced inflammatory responses are outweighed by the negative effects on renal blood flow.
- Studies have not been able to show benefit of treatment with antioxidants or dietary fatty acids.
- Monitoring blood pressure and proteinuria and trying to limit hypertension and proteinuria may be of benefit.
68
Why are stallion at reduced risk of cystitis than geldings?
Prostatic secretions contain a heat-stable cationic protein that has potent antibacterial activity.
69
List host defences in the bladder that protect against cystitis.
- Immunoglobulins in urine
- Mucopolysaccharide layer rich in glycosaminoglycans covering the uroepithelial surface
- Dilution with urine is initially useful however once the pathogens gain access to the bladder the rate of replication outweighs any dilution effect.
70
What protective mechanisms are there to avoid ascending cystitis?
Preputial and vulval flora protect against urethral colonisation but any anatomical defect that leads to turbulent urine flow compromises the maintenance of the normal flora and may increase likelihood of pathogenic colonisation. Once the distal urethra is colonised, ascending infection occurs rapidly to the proximal urethra and bladder which do not have a protective flora.
71
What are commonly implicated bacteria in cystitis?
E. coli, Proteus, Klebsiella, Enterobacter, Streptococcus, Staphylococcus, Pseudomonas aeruginosa and rarely Corynebacterium renale.
72
List treatments that may be of benefit in urinary acidification.
- Ammonia chloride
- Methionine
- Vitamin C
- Ammonium sulphate
- Adding grain to the diet (only modest decrease)
73
What have been the associated plants with epizootics of cystitis in USA and Aus?
Sudan grass and Johnson grass (hybrids of sorghum) resulting in sublethal intoxicatin with hydrocyanic acid causing demyelination of the lower spinal cord and bladder paralysis.
74
What are the protective mechanisms against ascending pyelonephritis?
- The intramural course of the ureters at their insertion into the bladder neck that prevents vesicoureteral reflux.
- The conical shape of the renal papillary duct openings in the renal pelvis that protects against intrarenal reflux which is required to initiate renal damage.
However, pyelonephritic scarring can develop after high pressure urinary tract obstruction, which may compromise these structures.
75
Differentiate the clinical signs of dysuria in pyelonephritis and cystitis.
Pyelonephritis: dysuria is manifest as haematuria and/or pyuria
Cystitis: dysuria is manifest as strnguria and pollakiuria
Other differentiating clinical signs include fever, weight loss, anorexia and depression in horses with upper UTI.
76
List common organisms associated with nephritis from haematogenous spread.
Actinobacillus equuli, Streptococcus equi equi, Rhodococcus equi, Salmonella.
77
What are the common parasites affecting the kidneys?
- Strongylus vulgaris (larval migration in the renal artery and parenchyma is considered aberrant but has been found in up to 20% in one abattoir study)
- Halicephalobus gingivalis (often life threatening due to concurrent CNS involvement leading to various neurological dysfunctions)
- Dioctophyma renale (large, bright red nematode with females reaching 100cm length - horse is an incidental host after ingesting annelid worms which are the intermediate host; once in the kidney the parasite can live 1-3yrs and sheds eggs in the urine. It completely destroys the renal parenchyma and death of the paraste leads to shrinking of the host kidney into a fibrous mass. Hydronephrosis or renal haemorrhage may be a serious complication.
- Klossiella equi (coccidian parasite) is common but no reports of clinical disease associated with infection.
78
Why are males more commonly affected by urolithiasis than females?
The shorter urethra of the female likely enables voiding of small calculi.
79
At what location can uroliths develop and where is most common?
Most common in the bladder (60%) although can also form in the kidneys (12%), Ureters (4%) and urethra (24%)
As many as 10% of affected horses had uroliths in multiple locations.
80
What factors contribute to precipitation of urinary crystals and nucleation to form uroliths?
Supersaturatoin of urine
Prolonged urine retention
Genetic tendencies to excrete large amounts of calcium
Uric acid
Oxalates
Presence of crystal promotors or inhibitors (inhibitors include pyrophosphate, nitrate, Mg, glycosaminoglycans and several glycoproteins; promotors include matrix substance A, uromucoid and a number of erum proteins)
81
What are the two basic forms of uroliths produced by horses?
Yellow-green spiculated stones that easily fragment, made primarily of CaCO3 (more than 90% are these)
Grey-white smooth stones that are resistant to fragmentation and contain phosphate in addition to CaCo3.
82
What factors make equine urine susceptible to stone formation?
Equine urine is typically alkaline which favours crystalisation of urolith components, especially CaCO3
83
What are the treatment options for lithiasis?
* Unless detected as an incidental finding before the development of CKD, treatment is realistically limited to horses with unilateral disease.
- Nephrotomy to remove the obstructing calculi (although may not result in improved renal function)
- Nephrectomy
- Ureterolithectomy vial ventral celiotomy or paralumbar approaches
- Basket stone dislodgers introduced via a vestibulo-urethral apprach for distal ureteral calculi
- Percutaneous nephrostomy to establish percutaneous urine flow has been done experimentally in one case
- Electrohydralic lithotripsy (converting electrical energy into mechanical energy to fragment the urolith.
84
What are the potential complications of standing perineal urethrotomy?
- Urethral trauma and stricture formation
- Urethrolith formation at the surgical site
- Development of a urethral diverticulum
- Persistent passage of urine throuhg a fistula at the surgical site
- Pararectal approach for dorsal cystotomy and electrohydraulic lithotripsy has been described.
85
What dietary manipulations can be made to decrease calcium excretion, promote diuresis and hence reduce recurrence of uroliths?
Changing the hay from alfalfa to grass or oat hay decreases the dietary calcium and hence should decrease urinary calcium excretion (faecal excretion is fairly constant).
Adjusting the dietary cation-anion balance to a lower DCAB by increasing grain in the diet, providing a low quality hay and adding ammonium chloride, calcium chloride or ammonium sulphate to the diet may help to acidify the urine and while this may increase the amount of Ca it should reduce the risk of forming calculi.
86
List common differential diagnoses for bladder paresis or paralysis.
- EHV-1 myelitis
- Polyneuritis equi
- Illicit tail block
- EPM
- Sacral fracture
- Osteomyelitis of the sacral vertebrae
87
What are the two types of bladder displacements in females and what displacements can occur in males?
- Extrusion through a tear in the vaginal floor
- True prolapse with eversion of the bladder
Note: urethral obstruction may also occur may occur with vaginal or uterine prolapse.
Males: Scrotal herniation of the bladder has been described
88
How do you distinguish glomerular from non-glomerular bleeding?
On microscopic examination, glomerular bleeding can be distinguished due to the presence of dysmorphism (marked variation in RBC size, shape and haemoglobin content) due to membrane deformation as erythrocytes traverse the glomerular filtration barrier. RBC or haemoglobin casts is also pathognomonic for glomerular bleeding.
89
What part of the penis is typically involved in urethral rents and why?
The corpus spongiosum penis, often at the level of the ischial arch.
Proposed to be due to a sudden decrease in intraluminal urethral pressure while pressure in the CSP is still high and once created, the lesion is maintained by bleeding at the end of each urination, allowing a fistula with the vascular tissue to be formed.
90
What treatment should be provided if any, in cases of urethral rent?
If there is evidence of anaemia or if bleeding persists for longer than 1 month a temporary sub-ischial urethrotomy has been successful in a number of geldings. The surgical wound takes several weeks to heal and is associated initially with moderate haemorrhage form the corpus spongiosum penis however haematuria should resolve within 1 week of the procedure. Limiting the incision into the corpus spongiosum penis but not into the urethral lumen has also been successful and is now the preferred treatment option, with reduced risk of urethral stricture formation, or fistula formation.
91
What are the hallmarks and diagnostic findings in idiopathic renal haematuria and differential diagnoses?
- Sudden onset gross haematuria, usually with passage of blood clots
- Can be life threatening haemorrhage
- Cystoscopy reveals no abnormalities but blood clots may be seen passing from one or both ureteral orifices
- DDX: renal adenocarcinoma, arteriovenous or aterioureteral fistula; also varicosities at the level of the vestibulovaginal sphincter in mares with reports of blood clots without further diagnostics being done (ie no cystoscopy).
* Arabians over represented (>50% of reported cases)
92
What diagnostics should be performed in cases of haematuria where the upper urinary tract is suspected?
- Urinalysis to determine whether there is concurrent cystitis and bacterial culture.
- Haematology and clinical chemistry
- Cystoscopy to determine the likely source of haemorrhage
- Renal ultrasound examination to rule out nephrolithiasis or ureterolithiasis; may sometimes see distended vascular space or renal vascular anomaly.
- Renal biopsy and immunofluorescent staining may help diagnose immune-mediated glomerular injury
* Tx with corticosteroids may be useful in cases with a suspected immune-mediated basis. If haemorrhage is severe unilateral nephrectomy may be indicated however haemorrhage can develop in the contralateral kidney.
93
List differentials for exercise-associated haematuria.
- Bladder erosions induced traumatically by the abdominal contents pounding the bladder against the pelvis during exercise
- Trauma secondary to uroliths
- Neoplasia and bleeding elicited from the impact of abdominal viscera during exercise
- Increased filtration of RBCs and protein across the glomerular barrier (occurs in humans and equids) - this is usually microscopic but can result in gross discolouration of urine in some case.
94
What are the cut-off values for PU/PD in horses (extrapolated from small animals)? And what needs to be taken into consideration when evaluating these numbers?
Urine output exceeding 50mL/kg/day and fluid intake exceeding 100mL/kg/day (equates to urine production of 25L and drinking 50L/day in a 500kg horse).
However, horses in hot weather, exercised hard or fed all hay diets may have water intake exceeding 100L/day but they will continue to produce a normal amount of urine.
95
After acute renal injury, during tubular repair is the urine likely to be isosthenuric, hyposthenuric or hypersthenuric?
Hyposthenuric as renal concentrating ability is impaired. Polyuria is a common and often temporary finding in horses that survive the acute phase of renal disease. Repair and return of concentrating ability may take several weeks, and a permanent reduction in total renal function may well persist.
96
What are the possible mechanisms of polyuria in case of CKD?
- Increased tubular flow rate in surviving nephrons, resulting in less time for water removal from tubular fluid
- Medullary hypertonicity may decrease due to diminished transport of Na and Cl out of tubular fluid passing through the ascending limb of the LOH along with increased blood flow through the remaining medullary tissue
- Impaired response of collecting ducts to vasopressin (acquired nephrogenic diabetes insipidus).
97
What are the treatment options for nephrogenic diabetes insipidus and neurogenic diabetes insipidus?
Nephrogenic: Restrict sodium and water intake or administer thiazide diuretics which inhibit sodium reabsorption in the distal tubule and increase solute delivery to the collecting duct. Tx with prostaglandin inhibitors or amiloride has also decreased polyuria in these patients. Replacement hormone therapy is ineffective.
Neurogenic: Tx consists of hormone replaced with vasopressin analogues such as desmopressin which can be administered via nasal insufflation. Other oral meds including chlorpropamide and clofibrate are also efficacious. Recovery or vasopressin activity is rare once the secretory neurons have degenerated to the degree that PU/PD become apparent.
98
What is a possible mechanism for polyuria in cases of endotoxaemia and sepsis?
Endotoxin-induced prostaglandin production (PGE2 is a potent vasodilating agent and antagonises the efffects of ADH on the collecting ducts.
99
What is renal tubular acidosis?
A syndrome of impaired renal acidification characterised by hypokalaemic hyperchloraemic acidosis without azotaemia. Frequently these horses have normal urinalysis.
100
What are the three types of renal tubular acidosis and their pathogenesis?
1. Classic or distal RTA arises from the inability of the cells of the distal tubule to establish a steep H+ excretion from the distal tubules. Accelerated K secretion occurs due to existing electrochemical driving forces in the distal nephron and lack of protons to offset them. These patients may also be hypercalciuric and hyperphosphaturic.
2. Proximal RTA is caused by failure of HCO3 reabsorption in the proximal tubule. Disruption of normal Na and H exchange or carbonic anhydrase activity results in excess flow of HCO3 to the distal tubule where the ability to resorb the anion is poor. This bicarbonaturia also results in accelerated K secretion hence hypokalaemia. However, eventually the distal tubule reaches a point at which it can handle the amount of HCO3 so the urine pH may start to decrease as HCO3 decreases and a new steady plasma HCO3 is established so acid-base homeostasis may return gradually, making this type of RTA usually self limiting.
3. This type has characteristics of Type 1 and 2 but is considered a variation of type 1.
101
How do you differentiate between proximal (type 2) and distal (type 1) types of renal tubular acidosis?
Based on measurement of urine pH - with Type 1, urine pH tends to stay within the normal alkaline range; with type 2, urine pH is generally neutral or slightly acidic. You can make this differentiation by assessing the urinary resposne to administration of urinary acidifying agents such as ammonium chloride which should lower the pH to less than 7.0 after oral administration. This occurs in normal horses and those with Type 2 RTA. If they have Type 1 or distal RTA the urine pH remains high despite the increased acid load. However as this will worsen acidosis in cases of type 2 RTA it is not recommended until at least partial HCO3 replacement has been attempted. Another test is to measure the urine net charge - if it is negative (ie Cl greater than the sum of Na and K) then type 2 RTA exists; if it is positive (sum of Na and K is greater than Cl) Type 1 RTA exists.
102
What are the common clinical signs of renal tubular acidosis?
Depression, poor performance, weight loss and anorexia. Less commonly chronic weight loss, ataxia, dysphagia and periodic collapse. The reduced K concentration can be associated with bradycardia.
103
What acid base/electrolyte finding suggests renal tubular acidosis?
Hyperchloraemic metabolic acidosis in the absence of extrarenal hypovolaemia such as diarrhoea or small intestinal ileus, and with a normal anion gap. Definitive diagnosis is based on demonstration of hypokalaemia and a urine pH that is neutral or alkaline in the face of severe acidosis (blood pH <7.15).
104
What is the treatment for renal tubular acidosis?
HCO3 and K replacement therapy - usually a combination of oral KCl and IV NaHCO3 and KCl. However you should not give NaHCO3 without some form of K supplementation to ensure that hypokalaemia does not get worse. Improvement is expected in 12-24 hours. Glucose should be added to IVFT to promote intracellular movement of K. K supplementation can probably be discontinued when the patient is appetent and discontinued when forage intake is normal. Long term oral NaHCO3 supplementation is often required for maintenance of normal acid base balance.
105
What are the primary renal neoplasms and associated findings?
- Renal adenoma (small circumscribed lesions in the renal cortex, usually incidental findings at necropsy).
- Renal cell carcinoma and adenocarcinoma (arise from the epithlium of the proximal convoluted tubules and often cause flank pain, gross haematuria and palpable renal mass - often poor performance, depresion, weight loss and recurrent colic. Usually unilateral). In one report 71% had haemabdomen and exfoliated cells in the peritoneal fluid. Frequently these tumours are large and adherent to adjacent vascular structures making removal difficult/impossible and metastases common.
- Nephroblastoma (Wilm's tumour) is an embryonal tumour that arises in primitive nephrogenic tissue or foci of dysplastic renal tissue.
- Transitional cell carcinoma arise from the uroepithelium of the renal pelvis or ureter.
- Squamous cell carcinoma arise from the uroepithelium of the renal pelvis or ureter.
- Dissemination of lymphosarcoma, haemangiosarcoma, melanoma or adenocarcinoma.
106
What are the common bladder neoplasms?
- Squamous cell carcinoma - squamous epithelial cells can be found in the normal equine bladder so this may explain why this tumour type is seen commonly.
- Transitional cell carcinoma
- Lymphosarcoma
- Leiomyosarcoma
- Rhabdomyosarcoma
- Fibromatous polyps
By the time clinical signs are observed most horses will have local metastatic involvement - most commonly to the aorta, iliac arteries, and lymph nodes, making the prognosis poor.
107
List common neoplasms of the urethra and external genitalia
- Squamous cell carcinoma
- Sarcoid
- Melanoma
- Mastocytoma
- Haemangioma
- Papillomata/warts
* Habronemiasis needs to be a differential as it can only be differentiated from SCC and sarcoids via microscopic examination.
108
What is the rationale behind the use of piroxicam as an adjunct to management of SCC?
It is a selective COX2 inhibitor and SCCs express COX2 (not all of them in equal amounts) and as such inhibition of COX2 may induce apoptosis in neoplastic cells, inhibit angiogenesis or act as an immunostimulant.
109
What are the main types of bladder dysfunction noted in horses and the differentiating factors?
1. UMN bladder - increased urethral resistance despite the presence of a full bladder (catheterisation may be difficult). Generally associated with broad, deep spinal cord lesions, hence its an uncommon problem as usually the additional clinical signs are not conducive with life. Exceptions are focal lesions caused by EPM, aberrant parasite migration etc. May develop reflexic urination due to stimulation of pressure receptors connected to pelvic nerve afferents which reflexively activate pelvic nerve efferents and pudendal nerve, hence detrusor contraction and striated urethral muscle relaxation. Urination is typically incomplete so sabulous accumulation is an issue and some urine dribbling may occur.
2. LMN bladder - paralysis/atonic bladder that becomes distended with relaxed urethral muscle hence you get urine dribbling with overflow. Incontinence tends to be continuous which helps differentiate it from UMN which is intermittent. Can be associated with lumbosacral trauma, EHV-1, polyneuritis equi, Sudan grass toxicity and sorghum cystitis. Tumours may be a differential too. Can be iatrogenic with alcohol tail blocks. Usually concurrent signs are loss of anal sphincter tone, tail paralysis, analgesia or hypalgesia over the perineum and atrophy of the hindlimb musculature with weakness. Damage to teh pudendal nerve and loss of external urethral sphincter integrity are particularly important. Penis or vulva may also be paralysed. Prognosis is usually poor.
3. Myogenic or non-neurogenic bladder typically occurs secondary to either mild neurologic dysfunction or musculoskeletal conditions that prevent posturing to urinate and complete emptying of the bladder. Hence with incomplete emptying you get progressive detrusor muscle atony and accumulation of urinary sediment. The weight and volume of this material in addition to urine stretches the detrusor muscle and eventually the crnail aspect of the bladder protrudes over the pelvic brim, displacing sediment cranio-caudally and exacerbating stretch, hence normal contraction and micturition are not possible. In addition, stretching results in breakdown of tight junctions that prevents depolarising waves from passing from muscle fibre to muscle fibre. When overdistention extends beyond the ability to maintain sphincter function incontinence develops. Part of the myogenic atony may stemo from secondary cystitis which develops after urinary retention due to urea conversion to ammonia which irritates the mucosa.
4. Urge incontinence - irritation of stretch receptors in the bladder wall with cystitis cause regular stimulation of stretch receptors in parasympathetic afferents and stimulates detrusor contractions that cannot be inhibited voluntarily, resulting in pollakiuria.
110
Describe innervation to the bladder.
- Somatic innervation is primarily to the striated muscle of the urethra via a branch of the pudendal nerve from S1-S2.
- Sympathetic nerve supply is via the hypogastric nerve with preganglionic fibres arising from L1-L4, synapsing in the mesenteric ganglion and synapsing in the caudal mesenteric ganglion. From here they supply the bladder via B2-receptors and proximal urethra via A1 and some A2 adrenergic receptors.
- Parasympathetic innervation originates in the sacral cord with neurons combining to form the pelvic nerve.
Due to many complex inter-neuronal connections between the different pathways complete denervation of the bladder is virtually impossible.
111
Describe the neurogenic control of micturition
- During filling the smooth and striated muscles remain contracted to maintain the internal and external urethral sphincters, and prevent urine leakage. This phase is dominated by sympathetic nerve activity. The detrusor muscle relaxes due to A-receptor-mediated inhibition of pelvic nerve afferents and stimulation of sympathetic B2 receptors in the smooth muscle of the bladder body (reflex from sensory input from stretch receptors via afferent pelvic nerve fibres to the sacral spinal cord. inter neurons in the cord and pre and post-ganglionic sympathetic fibres of the hypogastric nerve). As the bladder fills, intra-vesicular pressure rises once the detrusor muscle fibres are stretched fully. This stimulates bladder wall receptors with transmit an impuse via the pelvic nerve and ascending spinoreticular cord tracks to the pons, cerebrum and cerebellum where they are interpretted.
- Signals for voluntary micturition originate in the cerebrum and exert effects via the brainstem via UMNs that descend the reticulospinal tracts to the sacral parasympathetic nuclei to trigger emptying.
- From the sacral segments, pelvic nerve impuses stimulate detrusor muscle contraction and action potentials travelling via the parasympathetic ganglia in the pelvic plexus or bladder wall to postganglionic fibres stimulate smooth muscle contraction over the bladder. Simultaneous inhibition of the pudendal nerve and A and B2 sympathetic activity further facilittates detrusor activity and relaxation of the external and internal urethral sphincters. Detrusor muscle contraction pulls the bladder neck open and micturition occurs.
- The emptying phase ends when the bladder stretch receptors sense the bladder is empty and afferent parasympathetic impulses in the pelvic nerve cease. Pelvic nerve efferent activity also stops an dpudendal motor and sympathetic activity resumes due to lack of inhibition hence the detrusor muscle relaxes restoring the external and internal urethral sphincter tone.
112
What is the normal threshold of intravesicular pressure for detrusor muscle contraction?
90+/- 20cmH20.
113
List treatment options for bladder dysfunction
- General nursing, hygiene etc to minimise scald etc.
- Promotion of bladder emptying with regular catheterisation or indwelling (need to think about risk of infection)
- Bladder lavage to remove sabulous material
- A-adrenergic blcker phenoxybenzamine to eliminate urethral resistance and facilitate emptying in UMN or atonic over-distention.
- Bethanechol chloride, a parasympathomimetic that is resistant to action of acetylcholinesterase and has selective effects on smooth muscle of the GIT and bladder. Stimulates detrusor muscle activity by stimulating post-ganglionic parasympathetic effector cells rather than motor end plates. However this has no effect when the bladder is completely atonic or areflexic.
- Diazepam and dantrolene may be helpful in relaxing the urethra via A-adrenergic blockade
Overall the prognosis is generally fairly poor due to irreversible changes in the bladder wall.
