Homeostasis Part IA – VETERINARY CASE EXAMPLES
Dr Penny Watson (predominantly small animal)
Many of these case examples have accompanying PowerPoint slides with
radiographs on them, which will be made freely available to other supervisors on
Small breed dogs such as Yorkies are often affected with a condition called ‘collapsing trachea’. This is a useful example to discuss why the larger airways have cartilage rings. These dogs are born with weak dorsal tracheal cartilage which means that the thoracic trachea dilates during inspiration and compresses on expiration. The cervical trachea does the opposite (radiographs are available). This illustrates pressure changes in the thorax on inspiration and expiration and how the larger airways move with the chest wall (whereas
the vessels in the alveolar walls would do the opposite and collapse on inspiration). It is also useful to talk about equal pressure points and what a disaster it is if the airways where the EPP is do not have rigid walls. These dogs with collapsing tracheas get severe lower airway disease because they are constantly inspiring against a collapsing cervical trachea which greatly increases the work of breathing. This eventually leads to ‘corpulmonale’ ie right sided heart failure secondary to chronic pressure overload cause by pulmonary hypertension associated with chronic hypoxia. You can cure this by using a
stent in the trachea to ‘replace’ the damaged rings. However, many of these dogs already have permanently damaged lungs with emphysema due to the chronic respiratory difficulties before this is done.
Dogs and cats get ‘pyothorax’ – pus in the pleural space (radiographs supplied). This is really quite common in dogs and cats (same as ‘empyema’ in humans). In cats, it is often due to a cat bite in the chest wall. In dogs, usually a migrating grass seed – often inhaled which makes its way in to the lungs via the airways and then out to the pleura. We can use this to discuss lung volumes and the limitations of increased respiratory rate – as the pus builds up, you reach a limit where you cannot manage just by increasing ventilation
rate - when you just ventilate the dead space, you die!
It is also interesting to discuss dogs panting: if you look on pubmed, there are a number of references to people investigating panting dogs. Dogs pant to cool down – but they only ventilate their dead space while panting, so why don’t they die? (Normal deep breathing is superimposed on the panting – it is also the case that they DO ventilate a small amount of alveolar space when panting so they DO get a mild respiratory alkalosis – but not severe – whereas if they DID pant a large amount of alveolar air they WOULD get a respiratory alkalosis – which would be a problem, and would limit the panting – but this discussion is for later!) The other interesting thing about panting is that someone worked out that the amount of heat produced in contracting the respiratory muscles to
make a dog pant is greater than the amount of heat dissipated by the panting – so how does it work as a method of heat loss? It turns out that dogs reduce the work of panting by panting at the resonant frequency of their chest wall – so any one size of dog always pants at the same frequency regardless of how hot they are: if they are very hot, they pant all the time; if they are less hot, they pant intermittently but still at the same frequency (not slower) – if you look, small dogs and cats pant with a much higher frequency than big dogs and cats.
Foals: dysmature foals are relatively common especially amongst race horses – born full term but immature for term – one problem is respiratory distress due to insufficient surfactant – just like premature babies.
Feline asthma: (radiographs supplied) – a good example as it is very similar to human asthma – and we can even train cats to use inhalers (we use pediatric spacer-type devices – you can’t train them to inhale at the right time, so we treat them like babies!)
Paraquat poisoning – radiographs supplied – this occurs in dogs intermittently: usually as a result of dogs accidentally eating ‘laced’ carcases put out by game keepers to kill foxes. As in humans, it causes production of oxygen free radicals in the lungs and thus interstitial pulmonary oedema due to oxidant damage to alveoli (as well as acute renal failure). It is almost invariably fatal and there is not treatment. This is a good example to use to talk about the effect of oedema on O2 and CO2 and alveolar-arterial gradient. This dog’s blood gases are shown below and are also a good example of what happens when the diffusion distance in the lungs is increased. It is important to note that the dog is NOT
at altitude. It is a good example of how pO2 goes down with diffuse interstitial lung disease but CO2 also goes down as it is 20 x more soluble than O2 so less limiting – and the tachypnoea associated with the low O2 increases ventilation rate and thus flushes out CO2.
Under GA with 100% O2: would expect 4 x the O2 of room air ie approx 400mmHg. The high pCO2 suggests we are not ventilating the patient enough….but the fact that O2 has at least gone up shows that the problem is one of diffusion and not, for example, an upper airway obstruction or pulmonary thromboembolus, when increasing inspired O2 would have
not effect on arterial O2. You can use these also to discuss partial pressures of gases and what this means.
Examine the arterial blood gases given below and outline what you think might be going on with this dog. What would you expect to be the normal range for pO2 for a normal dog breathing 100% oxygen under general anaesthetic.
9 year old west highland white terrier dog (from Cambridgeshire!)
Arterial blood gases:
Room air: pO2 = 75 mmHg (normal 85-100)
pCO2 = 31 mmHg (normal 35-45)
General anaesthetic on 100% oxygen:
pO2 = 254 mmHg
pCO2 = 53 mmHg
Another good example of a disease affecting diffusion of gases between the alveolus and capillary is the pulmonary oedema in left-sided congestive heart failure. The commonest form of heart disease in small breed dogs (such as Cavalier King Charles spaniels) is mitral valve disease due to endocardiosis ( = myxomatous degeneration of the mitral valve – up to 80% of middle-aged to older Cavaliers end up affected). The main problem is back leakage
of blood in to the lungs in systole through the incompetent valve leading to increased pulmonary venous pressure which initially dilates pulmonary veins ( - you can discuss how they can compensate for a moderate increase in pressure as they are so compliant + open up more veins in parallel) then fluid leaks in to the interstitium then eventually in to the alveoli.
There are plenty of veterinary anaesthesia examples which can be discussed: we use similar monitoring equipment to humans (often the same). A good one is to discuss capnography:
why we use capnographs measuring inspired/expired CO2 to decide if our patient is well enough ventilated – why don’t we measure inspired/expired oxygen? From this, we can end up deriving the alveolar gas equation using CO2… Oxyglobin (illustrated by a picture – taken by me) – this is licensed for veterinary use (but not yet for human use, as far as I know). It is polymerised bovine haemoglobin which is used as an emergency therapy for very anaemic dogs – eg after severe haemorrhage or autoimmune haemolytic anaemia (see below). It can be life-saving, but is only a temporary measure while we find a suitable canine blood donor – why? This is a great example to discuss why we need RBCS. Problems with oxyglobin:
• Very short life in the plasma as filtered out quickly by the kidneys – the Hb is
polymerised to increase its life-span in the plasma (without that, the small Hb
molecules would be filtered out very quickly) but it still only lasts about 12 hours
• Free Hb supplies considerable colloid OP (which it does not if within RBCs) so
giving this iv can increase fluid in the vascular space and thus BP quite considerably – especially if the patient is already over-volume expanded (like the example below).
• No ‘micro-environ’ of the RBC – no carbonic anhydrase, MetHb reductase etc so no good for CO2 carriage and all the Hb will eventually end up oxidised and thus no good
• Also, related to above, no 2,4-DPG – could be a problem BUT bovine Hb was
chosen because, unlike human, it is NOT 2,4-DPG dependant
• The manufacturers originally claimed that oxyglobin would be great in trauma
patients because it would get into the small capillaries in injured tissues much better than red blood cells because of its smaller size (they even produced video cartoons to show this happening…) but in fact, it turned out that oxyglobin perfuses small capillaries LESS well than intact red cells: this was to be expected: why? (Fahraeus- Lindqvist effect).
An example of a case when we might use oxyglobin if we could find no suitable canine blood donor is a dog with autoimmune haemolytic anaemia (pictured in a slide): antibodies are produced against red blood cells which either coat them and increase their removal by splenic macrophages or, in severe cases, fix complement and ‘explode’ the red cells in the circulation. This is quite common in dogs – but unusual in this breed. We would be more likely to see it in spaniels which seem to have a ‘susceptible’ genetic make-up. This case to
discuss many things (again a great case) – again, why we need red cells – also the life span of a normal red cell (dogs are like humans – about 120 days). Other points to discuss:
• This dog has a packed cell volume (PCV) = haematocrit of 10% (normal dog PCV approx 35-40%) – below 10%, organs become hypoxic so we need to give a blood transfusion. The dog is hypoxic but not cyanotic – why? (because to see cyanosis you need a certain concentration of deoxyHb – don’t see it in anaemic patients because not enough Hb!)
• This dog’s tissues are poorly oxygentated – but how will we measure this? PO2 will be normal so measuring arterial blood gases of no help; Hb is fully saturated so using a pulse oximeter to measure Hb saturation no good…in fact, the only way to know is to measure its red cell count/packed cell volume ( on the same logic: giving this dog nasal oxygen is also not going to help – its haemoglobin is already fully saturated).
Cats’ red cells have significantly shorter life span than humans and dogs and are also more susceptible to oxidant damage – the two are likely related – oxidised red cells are likely removed more rapidly by the splenic macrophages. Cat red cells have a life span of only about 60 days. They have more exposed sulphahydryl groups on their Hb which become oxidised. Cats are much more susceptible to oxidising toxins than dogs or humans ( - like paracetamol: never give your cat a paracetamol!) However, dogs are susceptible to oxidising
toxins in onion which will haemolyse their red cells – enough in the onion on a pizza to kill a dog.
I will also put on the web an interesting case report of a puppy with a congenital metHb reductase deficiency – interesting but rare! Lots of interesting points in here which can be used for discussion (for example, what happens if you shake blood in room air which is cyanotic due to a respiratory problem vs this pup’s blood – see case report).
This is an interesting paper for discussions on pulmonary circulation and how it is NOT affected by the autonomic nervous system in the same way as the systemic circulation – it is pretty ‘autonomous’ in its responses (what makes pulmonary arteries constrict?) Pulmonary hypertension can be very serious and rapidly fatal (why?) in animals and humans – commonly in humans it occurs in premature infants. In dogs, even in the UK, it is commonly due to a type of heartworm called ‘angiostrongylus vasorum’ which lives in the main pulmonary arteries of dogs – they become infected by eating larvae in an intermediate
host (slugs and snails) – larvae migrate from the guts in to the circulation and thence to the pulmonary arteries. Their presence produces a reaction which causes end-artery vasoconstriction in the lungs (they also trigger intravascular coagulation often causing clotting defects in affected dogs). Sildenafil is of course Viagra – a long search for an effective drug for pulmonary hypertension in humans produced this, which is often used in premature babies. We are also starting to use it in dogs.
J Vet Intern Med. 2007 Nov-Dec;21(6):1258-64.Links
Sildenafil citrate therapy in 22 dogs with pulmonary hypertension.
Kellum HB, Stepien RL.
BACKGROUND: Pulmonary hypertension (PH) is a disease condition
characterized by abnormally increased pulmonary artery pressures and often is
associated with a poor prognosis. Sildenafil is a phosphodiesterase inhibitor that causes pulmonary arterial vasodilation and reduction in pulmonary artery
pressures. HYPOTHESIS: Treatment with sildenafil will improve
echocardiographic determinants of PH in dogs, while also improving quality of life and survival. ANIMALS: Twenty-two dogs with clinical and echocardiographic evidence of pulmonary hypertension. METHODS: A retrospective study evaluating the effects of sildenafil on physical examination, ECG and radiographic findings, blood pressure and echocardiographic findings of PH, clinical score, and outcome was completed. PH was defined as a peak tricuspid regurgitation flow velocity > or = 2.8 m/s or a peak pulmonic insufficiency flow velocity > or = 2.2 m/s. RESULTS: Sixteen of 22 dogs with PH were elderly females of small body size. Their clinical score was significantly improved (P = .0003) with sildenafil treatment, but physical examination findings remained unchanged. Heart rate, respiratory rate, vertebral
heart size, ECG heart rate, and systolic blood pressure did not change significantly with sildenafil treatment (P > .05). Peak tricuspid regurgitation flow velocities did not change significantly with the treatment of sildenafil, but selected systolic time intervals were significantly improved. Survival times for all dogs ranged from 8 to > 734 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Sildenafil did not significantly lower the degree of measurable PH in dogs. Clinical improvement and increased quality of life was seen with sildenafil treatment, despite lack of significant change in other variables.
To discuss clearance: there is a radiograph of a dog’s kidneys after it was given iohexol. This is an intravenous iodine-containing contrast agent used in dogs (and humans) to highlight the kidneys so we can see if there are any filling defects caused by eg tumours or infarcts. It is freely filtered, not secreted or reabsorbed – so, in fact, could be used to measure clearance in the same way as inulin. In fact, we are developing this as an alternative measure of GFR in dogs and also humans – we are working with collaborators at Addenbrookes to use iohexol clearance to measure GFR – the major issue was the technical
one of measuring iohexol concentrations in the blood which apparently was difficult, but this is being overcome and this may take over from the inulin clearance test eventually.
Oxalate stones in the ureter of a cat (there is radiograph): actually, about 80% or more of all urinary tract calculi in dogs and cats are in the bladder, not the kidneys (which is opposite to humans) but they do occasionally get renal calculi and have the same problems with them moving down the ureters as humans. This is a good case example to discuss what would ‘stop’ GFR ie ‘pre-renal’ causes (big drop in pressure of the afferent arteriole below range of autoregulation); ‘renal’ causes and ‘post-renal’ causes (like this case – complete blockage downstream leading to increased hydrostatic pressure in Bowman’s capsule).
Sometimes, vets accidentally tie of one ureter when spaying a bitch – this shouldn’t happen, but does sometimes – but they would be very unlucky to tie off both! Tying off one is not a problem from the point of view of renal clearance as the other kidney compensates, but the end result is often loss of the affected kidney. Discussing the hypothetical example of tying
off BOTH ureters shows us what the kidneys function most importantly as an ‘over-flow’ or chief excretor of – dogs are like people: potassium would go up acutely as the kidneys are the main place this is excreted; likewise phosphate (but NOT calcium) and also H+ ions and urea (and then creatinine – this takes longer as it is not produced as much as urea and is also a bigger molecule so does not diffuse from the obstructed kidneys and equilibrate with blood
as quickly as urea). The dog would likely die due to the increased potassium causing cardiac arrest (and if that didn’t get it, the H+ ions would…). The phosphate is of no immediate danger – but is measured elevated in the blood in acute (and chronic) renal failure.
A case example of a 7 year old entire male English bull terrier with chronic renal failure. The causes of kidney failure in dogs are usually unknown and are often primarily interstitial nephritis (as in cats) although some are glomerular disease. This dog had a 6 month history of polydipsia-polyuria, partial anorexia and intermittent vomiting bile. Blood samples showed:
• Urea 49mmol/l (normal 3.3-6.7)
• Creatinine 485 mmol/l (70-170)
Note that increases in urea and creatinine are a very poor measure of GFR – they only start to rise once 75% of kidney function has been lost – hence the drive to find a more sensitive measure of GFR (see above!)
Dog and cats are sometimes prescribed angiotensin-converting enzyme inhibitors (ACE-I) – just as are people. In dogs, they may be prescribed to treat hypertension (as in man) and also in congestive heart failure as they reduce the afterload by counteracting the compensatory rennin-angiotension-aldosterone system in heart failure (more on this later). ACE-I also
affect renal blood flow – ACE-I dilate the efferent arteriole more than the afferent (ie the opposite effect to rennin – which is what you would expect!) – This is useful in hypertension as it protects the glomerulus from damage by increased pressure in the incoming arteriole.
The disadvantage of this is that it reduces GFR IF the animal has low blood pressure in the afferent arteriole in heat failure– usually, this is not a problem because in the heart failure case, the overall increase in cardiac output associated with the reduction in afterload compensates – BUT we carefully monitor blood urea and creatinine concentrations of animals on ACE-I – especially for the first few days of therapy – to make sure we are not
reducing GFR to much.
‘Fanconi syndrome’ is a disease of the proximal convoluted tubules reported in dogs (and people) characterised by diminished re-absorption of solutes in the PCT. What substances would you expect to find in increased concentration in the urine of Fanconi syndrome suffers? Glucose (but NOT diabetic – blood glucose normal); amino acids; phosphate; bicarbonate (proximal tubular acidosis)
There is a picture of cystine crystals in the urine and two dog breeds which are
susceptible to – description under the picture (in powerpoint).
Potassium and cats: chronic kidney failure is very common in old cats – commoner than in dogs or people. We all know about cats’ kidneys being able to concentrate urine much more than dogs ( - they are ‘desert animals’ like Gerbils and have long loops of Henle).
Older cats usually get kidney failure due to interstitial nephritis (glomerulonephritis is very uncommon in cats). Inflammation and fibrosis of the interstitium interferes with the blood supply and the concentrating gradient and sodium pumps do not work so well – so the net result is that the cat becomes polyuric (passes a lot of urine – which is poorly concentrated (but note NOT dilute – actively diluting urine also requires a functioning nephron – so the osmolarity of the urine in renal failure approximates that of plasma) and
so also polydipsic (drinks a lot!) Cats are interesting as they are particularly susceptible to hypokalaemia (low blood potassium) in chronic renal failure – much more so that dogs orpeople – and we see this frequently in the clinics. Hypokalaemia gives them a hypokalaemic mypopathy – and the most distinctive feature in cats is that they cannot lift their heads properly so walk around with a drooped head. You can use this to discuss again the effects of low serum potassium on muscle function – and why. Why are cats so
susceptible? It seems to be because potassium loss in their kidneys is particularly flow dependant ie the increased flow of water through the tubules in chronic renal failure markedly increases potassium excretion. That alone is enough in many cats, but if you combine that with potassium loss in the vomiting induced by kidney failure and reduced intake caused by the appetite loss in renal failure, you have many reasons for their low potassium.Of cause, acute renal failure in a cat would cause INCREASED blood potassium just as
in dogs and humans but we see this less often – one cause of acute intrinsic renal failure sometimes seen in cats is ethylene glycol poisoning: anti-freeze – most commonly seen in cold parts of the US (occasionally in the UK) and especially in the Autumn when people empty out and refill their car radiators – if they leave the old radiator fluid with antifreeze lying around, cats love to drink it because it is sweet tasting: the result is a lot of oxalate crystals in the kidneys which cause severe damage. Many cats with this die – it is
unusual for them to recover. Dogs can get acute renal failure eating grapes ( grape toxicity) – although we do not yet know what the toxic ingredient of grapes actually is in dogs.We use the same diuretics in veterinary medicine as in humans: furosemide (frusemide) is our favourite – a powerful loop diuretic. Competitive luminal block Na+-K+-2Clcotransporter thick ascending limb (competes with Cl-). Most effective diuretic at low GFR (thiazides are not) so our preferred diuretic to ‘kick start’ the kidneys in acute renal shut down associated with shock (if this doesn’t work, we move on to mannitol). It is also
our preferred diuretic in congestive heart failure BUT usually only combined with an ACE-I if we are going to use it long term – if we don’t combine with an ACE-I, you get a compensatory increased in rennin-angiotensin-aldosterone release as the frusemide reduces circulating fluid volume (see below on discussion about congestive heart failure).
Aldosterone antagonists are also used – but mostly for the fluid build up in liver failure – see Volume regulation examples.
Clinical example of diabetes insipidus: We have a collie dog in the hospital which is drinking and urinating a lot. We suspect, as a result of our other investigations, that it might have central diabetes insipidus or nephrogenic diabetes insipidus or psychogenic polydipsia ( - i.e. drinking a lot just because it wants to - quite common in collies).
What would you expect to find if you measured urine and plasma osmolality
and endogenous ADH concentrations in each case? Design a simple test to
perform on the dog to differentiate between these conditions.
Central and nephrogenic DI: urine osmolality low (dilute); plasma osmolality usually slightly high because it is hard for the dog to drink enough to make up for the lack of ADH release or action Psychogenic polydipsia: plasma osmolality low and urine osmolality also low.
We do a water deprivation test: remove the dog’s water, empty its bladder, weigh it then keep weighing it and collecting urine until it either concentrates its urine(psychogenic) or loses 5% of its body weight because it can’t (DI) – then give it desmopressin and if it concentrates its urine then, it has central DI, whereas if it doesn’t, it has nephrogenic DI (problem with response to ADH in kidneys). Actually, in practice we usually have to do a‘modified’ water deprivation test and remove water gradually over a few days + salt load
dog by adding salt to its food – because the preceding polydipsia-polyuria (of any causes) ‘washes out’ the renal concentrating gradient.
These arterial blood gas values were obtained from a 9 year old Lhasa Apso dog with diabetic ketoacidosis (clue!) and acute pancreatitis. These values are almost incompatible with life (and in fact it died a few hours later, in spite of intensive care). Try to explain what is going on and why. What do you think we tried to treat this dog with? (Apart from insulin…)
pH 6.70 (normal 7.35-7.45)
pO2 = 84 mmHg (normal 85-100)
p CO2 = 29.3 mmHg (normal 35-45)
- = 3.7 mmol/l (normal 21-27)
Explanation: this dog is very acidotic – it is the lowest pH I have ever seen in a dog which is still alive (and in fact it died soon after I saw it – while we were trying to treat it). You can tell it is a metabolic acidosis with attempted respiratory compensation – the bicarbonate is vey low (hence metabolic acidosis) the pCO2 is also low – attempting to blow off the acid. The reason this dog has failed is because it has run out of buffer – this is a very very low bicarb – the ketoacids, combined likely with lactic acid associated with the severe inflammatory reaction with the pancreatitis, have used up all the buffer. Sadly, it will take a day or more for the kidneys to regenerate this bicarbonate and this dog has not got a few days – we would need to give it buffer by carefully supplementing bicarbonate intravenously – I was calculating the dose when the dog died….
There are some powerpoint slides with endoscopy in dogs – again, annotated in notes sections. Some diseases are characterised by diarrhoea which is primary caused by disordered gut motility (e.g. hyperthyroidism in cats – and maybe people too?!) What are the two main types of small intestinal motility and how might disruption of these result in diarrhoea?
Peristalsis and rhythmic segmentation –
most clinical cases of diarrhoea in dogs (as well as people) are caused by a decrease in RS rather than an increase in peristalsis – the latter, when unopposed by RS, results inrapid movement of ingesta down the gut and thus diarrhoea – note the best antidiarrhoeals are actually opiates (like lopermide) which act by increasing RS. (The exception is the diarrhoea associated with severe intestinal parasite infestations which triggers big peristaltic waves in an attempt to get rid of the parasites)