Veterinary · Pre-clinical and foundation · also MSVE VPB-111
How blood, heart, lungs and kidneys keep the internal environment stable in mammals and birds. Acid-base and fluid balance here underpin fluid therapy in the clinic.
In the exams: ICAR AICE-JRF core group 08; ICAR AIEEA-PG 14 (Physiology); PRC 10%; Nepal NLEV 6; China basic paper 13; AVE Paper 1 at least 5
Veterinary physiology is the study of how the healthy animal body works. This first course covers the systems that keep the internal environment steady: the cell membrane and its transporters, the body fluid compartments, blood and clotting, the heart and blood vessels, the lungs and the carriage of oxygen and carbon dioxide, the kidney, water balance and acid-base balance. Most diseases disturb one of these controlled variables, and most drip-line treatments try to restore one.
The subject is multi-species. A dog, a dairy cow, a horse, a hen and a camel solve the same physical problems in different ways. This manual states the mammalian principle first and then the species differences a practitioner needs.
Reference values in physiology differ between species, breeds, ages, laboratories and analysers. This manual therefore gives ranges only where they are standard textbook teaching and asks the reader always to use the reference interval of the laboratory that ran the sample. Worked calculations are shown step by step, because examiners ask for them and clinicians use them daily.
Worldwide it is examined as an early degree course (the Indian MSVE course VPB-111), as a named block in licensing papers such as the Philippine, Nepali, Chinese, Australasian and North American BCSE examinations, and as a core group in Indian postgraduate and PhD entrance tests.
Every cell is bounded by a lipid bilayer of phospholipids and cholesterol in which proteins float, the fluid mosaic model. Small uncharged molecules such as oxygen, carbon dioxide and urea cross the bilayer by simple diffusion, whose rate follows Fick's law: it rises with the concentration gradient, the surface area and the permeability, and falls with membrane thickness. Ions and polar molecules need proteins. Channels form water-filled pores that may be gated by voltage, by a ligand or by stretch. Carriers bind their substrate and change shape; when they move it down its gradient the process is facilitated diffusion (glucose through GLUT transporters), which shows saturation, specificity and competition. Primary active transport uses ATP directly. The sodium-potassium ATPase moves three sodium ions out and two potassium ions in for each ATP hydrolysed, so it is electrogenic and it builds the gradients that the rest of the cell spends. Secondary active transport uses the sodium gradient to drive another solute: sodium-glucose cotransport (SGLT) in the intestine and proximal tubule, and sodium-hydrogen exchange as an antiporter. Water crosses mainly through aquaporins.
Because the membrane is far more permeable to potassium than to sodium at rest, potassium leaks out down its gradient and leaves the inside negative. The equilibrium potential for any ion is given by the Nernst equation; at body temperature it simplifies to about 61.5 millivolts multiplied by the logarithm of outside over inside concentration for a monovalent cation. With 4 mmol/L potassium outside and 140 inside, the potassium equilibrium potential is about -95 mV; for sodium, 145 outside and 12 inside, it is about +67 mV. The resting potential of most nerve and muscle cells lies between about -70 and -90 mV, close to the potassium potential, and the Goldman-Hodgkin-Katz equation explains why: it weights each ion by its permeability. Hyperkalaemia, for example in a cat with urethral obstruction or a calf with severe diarrhoea and acidosis, depolarises the resting membrane, first increasing and then reducing excitability, and it slows cardiac conduction. An action potential is an all-or-none reversal of potential caused by opening of voltage-gated sodium channels, followed by repolarisation as sodium channels inactivate and potassium channels open.
Cells talk through chemical messengers. Water-soluble messengers such as catecholamines and peptide hormones bind surface receptors: G protein-coupled receptors that change cyclic AMP (through Gs or Gi) or raise intracellular calcium through phospholipase C, inositol trisphosphate and diacylglycerol; ion-channel receptors; and enzyme-linked receptors such as the insulin receptor tyrosine kinase. Lipid-soluble messengers such as steroid and thyroid hormones enter the cell and act on nuclear receptors to change gene transcription, so their effects are slower and longer. Most controlled variables are held by negative feedback: a sensor detects the deviation, an integrating centre compares it with a set point and an effector corrects it. Blood pressure, plasma osmolality, arterial carbon dioxide and body temperature all work this way. Positive feedback, in which the response amplifies the stimulus, is rarer and ends in a discrete event: the clotting cascade, the ovulatory LH surge and the Ferguson reflex at parturition.
Water is the largest single component of the body. In an adult lean mammal total body water is commonly taught as about 60 per cent of body weight, with wide variation: it is higher in neonates (often 70 to 80 per cent), lower in fat animals because adipose tissue holds little water, and lower in old animals. About two-thirds of total body water is intracellular fluid and one-third extracellular. Extracellular fluid is divided into interstitial fluid (roughly three-quarters of it) and plasma (roughly one-quarter), with a small transcellular fraction: cerebrospinal, synovial, pleural, peritoneal and ocular fluids, and the fluid in the gut lumen. In herbivores the gut fluid is not small. The rumen and the equine large colon hold a large reservoir of water and electrolytes that can buffer short-term losses, and that can also be sequestered in disease: fluid pooled in a displaced or twisted abomasum, or in an obstructed equine colon, is lost from the effective circulation even though it is still inside the animal. Blood volume is commonly taught as roughly 6 to 9 per cent of body weight depending on species, with the dog at the upper end and the cat and ruminants lower; exact values differ between textbooks.
A compartment is measured by the indicator dilution principle: volume equals the amount of marker given, less any amount lost, divided by its concentration once mixed. The marker must spread only through the compartment of interest. Total body water is measured with deuterium oxide, tritiated water or antipyrine; extracellular fluid with substances that stay outside cells, such as inulin, mannitol, thiocyanate or bromide; plasma volume with Evans blue dye (T-1824) or radio-iodinated albumin, which bind to plasma albumin; and red cell volume with chromium-51 labelled red cells. Blood volume follows from plasma volume and haematocrit: blood volume equals plasma volume divided by (1 minus the haematocrit as a fraction). If 10 mg of Evans blue gives a mixed plasma concentration of 0.004 mg/mL, plasma volume is 2,500 mL, and at a haematocrit of 0.40 the blood volume is about 4,170 mL.
The two major compartments differ sharply in composition. Extracellular fluid is rich in sodium, chloride and bicarbonate; intracellular fluid is rich in potassium, magnesium, phosphate and protein. Plasma and interstitial fluid are almost identical except that plasma contains much more protein, chiefly albumin, which gives plasma its colloid osmotic (oncotic) pressure. Water moves between plasma and interstitium across the capillary wall according to the Starling equation: net filtration is proportional to (capillary hydrostatic pressure minus interstitial hydrostatic pressure) minus a reflection coefficient times (plasma oncotic pressure minus interstitial oncotic pressure). With capillary pressure 30 mmHg, interstitial pressure 0, plasma oncotic pressure 25 and interstitial oncotic pressure 5 mmHg, the net outward pressure is 10 mmHg. Oedema forms when capillary pressure rises (right heart failure, brisket disease), when plasma albumin falls (protein-losing enteropathy, liver failure, heavy parasitism causing the bottle jaw of sheep with haemonchosis), when capillaries become leaky (inflammation, sepsis), or when lymph drainage is blocked. Water moves between the extracellular and intracellular compartments by osmosis, so sodium, the main extracellular osmole, sets the volume of the extracellular fluid while water balance sets its concentration.
Clinical dehydration is estimated from skin tent, eye position in the orbit, mucous membrane moisture, capillary refill and body weight. The deficit in litres is body weight in kilograms multiplied by the estimated percentage dehydration as a fraction: a 400 kg cow judged 8 per cent dehydrated needs about 32 litres to replace the deficit, before maintenance needs and ongoing losses are added. Losses are described as isotonic (diarrhoea, haemorrhage), hypotonic loss leaving the animal hypernatraemic (water deprivation, heat with panting) or hypertonic loss leaving it hyponatraemic (salt lost in excess of water, for example when a diarrhoeic calf drinks only water). Crystalloids distribute through the whole extracellular fluid, so only about a quarter of an isotonic crystalloid infusion stays in the plasma once it has equilibrated, whereas pure water, given as dextrose 5 per cent, distributes through total body water.
Blood is a suspension of cells in plasma. When blood is centrifuged in a microhaematocrit tube it separates into packed red cells at the bottom, a thin buffy coat of white cells and platelets, and plasma on top. The packed cell volume (PCV, haematocrit) is the fraction of blood occupied by red cells. Plasma is the fluid part of anticoagulated blood and contains fibrinogen; serum is the fluid left after blood has clotted and lacks fibrinogen and the clotting factors consumed in the clot. Plasma proteins are albumin, which provides most of the oncotic pressure and carries fatty acids, calcium, bilirubin and many drugs; globulins, which include transport proteins and immunoglobulins; and fibrinogen. Most plasma proteins other than immunoglobulins are made in the liver. Mammalian red cells are anucleate biconcave discs in most species; camelids have small oval red cells without nuclei, while birds, reptiles and fish have oval nucleated red cells. Red cell size differs greatly: goats and sheep have small red cells and the dog among the largest of the domestic species. Red cells are made in the bone marrow under the control of erythropoietin, which is produced mainly by peritubular interstitial cells of the kidney in response to reduced oxygen delivery. This is why chronic kidney disease causes a non-regenerative anaemia. The marrow needs iron, copper (for iron handling), cobalt (for vitamin B12, which in ruminants is synthesised by rumen microbes only if dietary cobalt is adequate), folate and protein. Haemoglobin is a tetramer of two alpha and two beta globin chains, each carrying an iron-containing haem that binds one oxygen molecule while the iron stays in the ferrous state. Red cells live for a set time and are then removed by macrophages, chiefly in the spleen; the life span is commonly given as about 100 to 120 days in the dog, shorter in the cat, and longer in the horse and in cattle, with much shorter life spans in birds.
Mean corpuscular volume (MCV, in femtolitres) equals PCV in per cent times 10 divided by the red cell count in millions per microlitre. Mean corpuscular haemoglobin (MCH, picograms) equals haemoglobin in g/dL times 10 divided by the red cell count. Mean corpuscular haemoglobin concentration (MCHC, g/dL) equals haemoglobin divided by PCV times 100. A dog with PCV 45 per cent, red cells 6.5 million per microlitre and haemoglobin 15 g/dL has an MCV of about 69 fL, an MCH of about 23 pg and an MCHC of about 33 g/dL. Because red cell size differs between species, an MCV that is normal for a goat would be severely microcytic in a dog; always use species-specific intervals. A regenerative anaemia shows polychromasia and reticulocytes on the smear, often with a raised MCV and a lower MCHC. Because the reticulocyte percentage looks higher simply because there are fewer mature cells, it is corrected: corrected reticulocyte percentage equals the observed percentage times the patient's PCV divided by a normal PCV. The horse is the exception: it does not release reticulocytes into peripheral blood even in a strong marrow response, so regeneration is judged from serial PCV, MCV or a marrow sample.
White cells are granulocytes (neutrophils, eosinophils, basophils), lymphocytes and monocytes. In the dog, cat and horse neutrophils usually outnumber lymphocytes in health, whereas in healthy adult cattle, sheep, goats and pigs lymphocytes are often the predominant cell, so a neutrophil-to-lymphocyte ratio that would look normal in a dog can mean stress or inflammation in a cow. Birds and reptiles have heterophils, with red rod-shaped granules, in place of neutrophils, and nucleated thrombocytes in place of platelets. Excitement and adrenaline cause a physiological leucocytosis and, in the horse and dog especially, splenic contraction that raises the PCV quickly; the equine spleen can store a large fraction of the red cell mass. Corticosteroid release or treatment gives the stress leukogram: neutrophilia, lymphopenia, eosinopenia and, in the dog, monocytosis.
Haemostasis is the arrest of bleeding. When a vessel is cut, it constricts, and platelets adhere to exposed subendothelial collagen. Adhesion under high shear depends on von Willebrand factor, a large multimeric protein made by endothelium and megakaryocytes, which bridges collagen and the platelet glycoprotein Ib receptor. Adhered platelets are activated: they change shape, release granule contents (ADP, serotonin, calcium, von Willebrand factor) and make thromboxane A2 through cyclo-oxygenase. Activation exposes the glycoprotein IIb/IIIa receptor, which binds fibrinogen and links platelets into an aggregate, the primary platelet plug. Aspirin blocks platelet cyclo-oxygenase irreversibly, so its effect lasts the life of the platelet. Defects of primary haemostasis give surface bleeding: petechiae, ecchymoses, epistaxis and prolonged bleeding from mucosa. The main causes are thrombocytopenia, platelet function defects and von Willebrand disease, which is the commonest inherited bleeding disorder of dogs and is recognised in several breeds, including the Dobermann. The buccal mucosal bleeding time tests primary haemostasis when the platelet count is adequate.
The platelet plug is stabilised by fibrin. The classical cascade divides the clotting factors into an extrinsic pathway (tissue factor and factor VII), an intrinsic or contact pathway (factors XII, XI, IX and VIII, with prekallikrein and high-molecular-weight kininogen) and a common pathway (factors X, V, prothrombin II and fibrinogen I). Factor Xa with Va converts prothrombin to thrombin, and thrombin converts fibrinogen to fibrin, activates factor XIII to cross-link it, and amplifies the cascade by activating V, VIII, XI and platelets. In the body clotting follows the cell-based model: initiation on tissue-factor-bearing cells makes a little thrombin; amplification on the platelet surface activates cofactors; propagation on activated platelets by the tenase (IXa-VIIIa) and prothrombinase (Xa-Va) complexes generates a burst of thrombin. Calcium is needed at several steps, which is why citrate and EDTA stop blood clotting. Factors II, VII, IX and X, and the anticoagulant proteins C and S, need vitamin K for gamma-carboxylation of glutamic acid residues. Anticoagulant rodenticides and the dicoumarol formed in mouldy sweet clover block recycling of vitamin K, so these factors fall according to their half-lives; factor VII has the shortest, so the prothrombin time lengthens first.
The prothrombin time (PT) tests the extrinsic and common pathways; the activated partial thromboplastin time (aPTT) tests the intrinsic and common pathways; the thrombin time and fibrinogen test the last step. Samples for these tests are collected into citrate in a fixed ratio of nine parts blood to one part anticoagulant, because under-filling dilutes the plasma and falsely prolongs the times. Haemophilia A (factor VIII deficiency) and haemophilia B (factor IX) are X-linked, so affected animals are usually male, and they prolong the aPTT with a normal PT. Factor XI deficiency is recognised in Holstein cattle. Factor XII deficiency, reported in cats, prolongs the aPTT markedly but does not cause bleeding, because contact activation matters little in the body. Birds have little contact-pathway activity and rely mainly on tissue factor. Bracken fern poisoning in cattle damages the marrow and causes thrombocytopenia with haemorrhages. Clotting is limited by natural anticoagulants. Antithrombin inactivates thrombin and factor Xa, and heparin accelerates it greatly. Thrombomodulin on endothelium binds thrombin and turns it into an activator of protein C; activated protein C, with protein S, destroys factors Va and VIIIa. Once a clot has done its job it is removed by fibrinolysis: tissue plasminogen activator converts plasminogen bound in the clot into plasmin, which digests fibrin into fibrin degradation products; D-dimers come only from cross-linked fibrin, so they show that clotting and lysis have both happened. Disseminated intravascular coagulation is a consumptive disorder in which widespread activation uses up platelets and factors, so the animal bleeds and clots at once; it complicates sepsis, heat stroke, neoplasia and gastric dilatation-volvulus in dogs, and endotoxaemic colic in horses. The laboratory picture is thrombocytopenia, prolonged PT and aPTT, and raised D-dimers and fibrin degradation products, with falling antithrombin.
Cardiac muscle cells are striated, branched and joined by intercalated discs containing gap junctions, so the atria and ventricles each behave as a functional syncytium. The heartbeat starts in the sinoatrial node, whose cells have no stable resting potential: a slow depolarisation during diastole (the pacemaker potential, carried by the funny current If through HCN channels and by T-type calcium channels) brings them to threshold, and the upstroke is carried by L-type calcium channels, not fast sodium channels. The impulse spreads through the atria to the atrioventricular node, where conduction is slow; this AV delay lets atrial contraction finish filling the ventricles. It then passes along the bundle of His, the bundle branches and the Purkinje fibres. The ventricular action potential has a fast sodium upstroke (phase 0), a brief repolarisation (phase 1), a long plateau (phase 2) maintained by calcium entry through L-type channels balanced by potassium exit, repolarisation (phase 3) and rest (phase 4). Calcium entering during the plateau triggers calcium release from the sarcoplasmic reticulum through ryanodine receptors (calcium-induced calcium release), and the strength of contraction depends on how much calcium is delivered to troponin C.
The cardiac cycle is the sequence from one beat to the next. In late diastole the ventricles fill passively through open atrioventricular valves, and atrial systole adds a final volume, which matters more at high heart rates and in horses at exercise. When the ventricles begin to contract, ventricular pressure exceeds atrial pressure and the AV valves close, giving the first heart sound. All valves are now closed: this is isovolumetric contraction, when pressure rises steeply at constant volume. When ventricular pressure exceeds aortic and pulmonary pressures, the semilunar valves open and ejection begins. As the ventricle relaxes, pressure falls below arterial pressure, the semilunar valves close, giving the second heart sound, and the dicrotic notch appears on the aortic pressure trace. Isovolumetric relaxation follows until ventricular pressure falls below atrial pressure and the AV valves open again. A third heart sound comes from rapid early ventricular filling and a fourth from atrial contraction; these are usually inaudible in the normal dog and cat, where a gallop rhythm suggests disease, but are commonly heard in normal horses. End-diastolic volume minus end-systolic volume is stroke volume; stroke volume divided by end-diastolic volume is the ejection fraction.
Cardiac output is heart rate times stroke volume. A dog with a heart rate of 100 per minute and a stroke volume of 25 mL has a cardiac output of 2.5 L/min. Stroke volume depends on preload, contractility and afterload. Preload is the stretch of the ventricle at the end of diastole; by the Frank-Starling mechanism, greater filling stretches the sarcomeres towards their optimal length and the ventricle ejects more, so the two ventricles match their outputs beat by beat. Contractility, or inotropy, is the force of contraction at a given preload; sympathetic stimulation through beta-1 receptors raises it by increasing calcium entry and uptake. Afterload is the load the ventricle must overcome to eject, largely arterial pressure. Cardiac output can be measured by the Fick principle: oxygen consumption divided by the arterial-mixed venous oxygen content difference. If oxygen consumption is 250 mL/min and the arterial and mixed venous contents are 20 and 15 mL per 100 mL, the difference is 50 mL per litre and output is 5 L/min. Mean arterial pressure is approximately diastolic pressure plus one-third of the pulse pressure at resting heart rates.
The electrocardiogram (ECG) records the summed electrical activity of the heart at the body surface. The P wave is atrial depolarisation, the QRS complex ventricular depolarisation and the T wave ventricular repolarisation; the PR interval is mainly AV nodal delay. Heart rate from a rhythm strip is 60 divided by the R-R interval in seconds: at a paper speed of 25 mm/s an R-R of 15 mm is 0.6 s, a rate of 100 per minute; the same 15 mm at 50 mm/s is 0.3 s, a rate of 200. Species differ in how the ventricles depolarise. In dogs, cats and primates, Purkinje fibres end in the subendocardium and depolarisation spreads from endocardium to epicardium in an orderly front, so QRS vectors reflect ventricular size, and chamber enlargement can be judged from the ECG. In horses, cattle, sheep and pigs, Purkinje fibres penetrate almost the full thickness of the ventricular wall, depolarisation occurs in bursts that largely cancel out, and the ECG is poor at detecting chamber enlargement but good for rhythm. Horses have high resting vagal tone, so second-degree atrioventricular block and sinus arrhythmia at rest are normal findings that disappear with exercise; respiratory sinus arrhythmia is also normal in the dog.
Flow through a vessel equals the pressure difference along it divided by resistance, the vascular version of Ohm's law. For the whole systemic circulation, cardiac output equals mean arterial pressure minus right atrial pressure divided by total peripheral resistance; because right atrial pressure is near zero, mean arterial pressure is roughly cardiac output times total peripheral resistance. Poiseuille's law shows that resistance is inversely proportional to the fourth power of the radius, so halving the radius of an arteriole raises its resistance sixteen-fold. That is why the arterioles, whose smooth muscle can change their radius, are the main resistance vessels and the site of control of both blood pressure and the distribution of flow. Veins are thin-walled and compliant and hold most of the blood volume; they are capacitance vessels, and venoconstriction shifts blood towards the heart and raises preload. Many organs hold their flow nearly constant over a wide range of perfusion pressure, a property called autoregulation, especially the brain, heart and kidney. Two mechanisms explain it. The myogenic response is the contraction of arteriolar smooth muscle when it is stretched by a rise in pressure. The metabolic theory holds that active tissue releases vasodilators (adenosine, carbon dioxide, hydrogen ions, potassium, lactate) and consumes oxygen, so flow matches metabolism; this active hyperaemia is the dominant control in heart and exercising muscle. Coronary flow to the left ventricle occurs mainly during diastole because systolic contraction compresses the intramural vessels, so tachycardia, which shortens diastole, reduces the time for myocardial perfusion. In the lung, low alveolar oxygen causes constriction of pulmonary arterioles, the opposite of the systemic response; this hypoxic pulmonary vasoconstriction matches perfusion to ventilation and is strong in cattle and pigs (see chapter 9).
Short-term blood pressure control is neural. Stretch receptors in the carotid sinus (afferents in the glossopharyngeal nerve) and the aortic arch (vagus nerve) fire faster when pressure rises. The signal reaches the nucleus tractus solitarius in the medulla, which inhibits the sympathetic vasomotor centre and excites vagal output. The result is slowing of the heart, reduced contractility and vasodilation, bringing pressure back down. A fall in pressure does the opposite: tachycardia, increased contractility, arteriolar constriction and venoconstriction. Sympathetic noradrenaline acts through alpha-1 receptors to constrict vessels and through beta-1 receptors to raise heart rate and contractility; adrenaline from the adrenal medulla also acts on beta-2 receptors that dilate muscle arterioles. Parasympathetic vagal fibres slow the heart through muscarinic M2 receptors. Baroreceptors reset to a new level within days, so they do not set long-term pressure. Long-term pressure depends on blood volume, which the kidney controls through sodium balance. When renal perfusion falls, sympathetic activity rises or the macula densa senses less sodium chloride, juxtaglomerular cells release renin. Renin converts angiotensinogen to angiotensin I, and angiotensin-converting enzyme, mainly in the lung, converts it to angiotensin II. Angiotensin II constricts arterioles, stimulates aldosterone release from the zona glomerulosa, stimulates thirst and antidiuretic hormone release, and increases proximal tubular sodium reabsorption. Aldosterone increases sodium reabsorption and potassium secretion in the distal nephron. Antidiuretic hormone (vasopressin) is released in response to raised plasma osmolality and to large falls in blood volume; it conserves water through V2 receptors and constricts vessels through V1 receptors. Atrial and brain natriuretic peptides are released when the heart is stretched and promote sodium excretion and vasodilation. In heart failure these systems, meant for haemorrhage, retain salt and water and worsen congestion, which is the rationale for blocking them.
Air moves because the respiratory muscles change the volume of the thorax. In mammals the diaphragm is the main inspiratory muscle, helped by the external intercostals; quiet expiration is largely passive recoil of lung and chest wall. Horses are an exception: they breathe biphasically, with an active expiratory phase driven by abdominal muscles and a passive part near the resting volume, and they are obligate nasal breathers because the soft palate normally seals the mouth off from the larynx. At the canter and gallop a horse takes one breath per stride, a locomotor-respiratory coupling that limits ventilation at maximal exercise. Compliance, the change in volume per unit change in pressure, depends on elastic tissue and on surface tension, which is reduced by surfactant from type II alveolar cells; premature neonates short of surfactant develop respiratory distress. Minute ventilation is tidal volume times frequency, but only alveolar ventilation takes part in gas exchange: alveolar ventilation equals (tidal volume minus dead space) times frequency. Dead space includes the anatomical dead space of the conducting airways and alveolar dead space from ventilated but unperfused alveoli. Panting animals take shallow, fast breaths that ventilate mainly dead space, which cools them by evaporation while limiting loss of carbon dioxide.
Breathing is generated by networks in the brainstem. The medulla contains the dorsal respiratory group, mainly inspiratory and receiving sensory input through the nucleus tractus solitarius, and the ventral respiratory group, containing the pre-Botzinger complex that generates the basic rhythm, and both inspiratory and expiratory neurons. Pontine centres (pneumotaxic and apneustic) smooth and time the transition between inspiration and expiration. Stretch receptors in airway smooth muscle send signals up the vagus that end inspiration when the lung is inflated, the Hering-Breuer inflation reflex, which is more important in many domestic species at rest than in adult humans. The dominant stimulus to breathing is carbon dioxide. Central chemoreceptors near the ventral surface of the medulla respond to the hydrogen ion concentration of the surrounding interstitial fluid and cerebrospinal fluid. Carbon dioxide crosses the blood-brain barrier freely, whereas hydrogen and bicarbonate ions cross slowly, so a rise in arterial carbon dioxide rapidly acidifies the cerebrospinal fluid and drives ventilation, while a metabolic acidosis acts at first mainly on the peripheral receptors. Peripheral chemoreceptors in the carotid bodies (glossopharyngeal nerve) and aortic bodies (vagus) respond to a fall in arterial partial pressure of oxygen, a rise in carbon dioxide and a fall in pH. Their response to oxygen is small until the arterial oxygen partial pressure falls below about 60 mmHg; they sense partial pressure, not content, so anaemia and carbon monoxide poisoning do not stimulate them much. In chronic hypercapnia the drive shifts towards hypoxia, and giving high oxygen can depress breathing. Birds have intrapulmonary chemoreceptors in the lung that are inhibited by carbon dioxide and so signal the carbon dioxide washout of each breath. Heat stress drives panting in dogs, sheep, cattle and poultry independently of blood gases, and the resulting fall in carbon dioxide causes respiratory alkalosis.
Birds breathe very differently. They have no diaphragm; the sternum and ribs move to change the volume of the air sacs, which act as bellows while the rigid lung barely changes size. Air passes through the parabronchi in the same direction during both inspiration and expiration: inspired air goes largely to the caudal air sacs, then through the lung to the cranial air sacs and out. Gas exchange takes place in tiny air capillaries around the parabronchi, and blood flows across the air stream at right angles, a cross-current arrangement that allows the partial pressure of oxygen in end-capillary blood to exceed that in the exhaled air, which is impossible in the mammalian alveolar lung. The blood-gas barrier is very thin. Because the air sacs move air, a bird restrained on its back or held with pressure on its keel may be unable to ventilate.
Oxygen and carbon dioxide cross the alveolar-capillary membrane by diffusion. Fick's law says transfer is proportional to the surface area and the partial-pressure difference and inversely proportional to thickness; carbon dioxide diffuses about twenty times faster than oxygen because it is far more soluble, so diffusion problems show first as low oxygen. Alveolar oxygen is predicted by the alveolar gas equation: alveolar oxygen partial pressure equals the inspired oxygen fraction times (barometric pressure minus water vapour pressure, 47 mmHg at 37 degrees) minus arterial carbon dioxide divided by the respiratory quotient (commonly 0.8). At sea level, breathing air with a PaCO2 of 40 mmHg, alveolar oxygen is about 100 mmHg. Regions with low ventilation for their perfusion behave like a shunt and lower arterial oxygen; regions with high ventilation for their perfusion behave like dead space. The difference between alveolar and arterial oxygen (the A-a gradient) widens when mismatch, shunt or diffusion impairment is present but not when low oxygen is due only to hypoventilation. In large animals under general anaesthesia in dorsal or lateral recumbency, the dependent lung collapses and shunt can be large, so a horse can be hypoxaemic even on oxygen.
Oxygen is carried in two forms. A small amount is dissolved, about 0.003 mL per 100 mL of blood per mmHg, so at 100 mmHg only 0.3 mL per 100 mL. Almost all is bound to haemoglobin, each gram of which can carry about 1.34 mL of oxygen when fully saturated. Arterial oxygen content therefore equals 1.34 times haemoglobin times saturation plus 0.003 times PaO2. A dog with haemoglobin 12 g/dL, saturation 97 per cent and PaO2 95 mmHg has about 15.9 mL per 100 mL. Anaemia lowers content without changing PaO2 or saturation. The oxyhaemoglobin dissociation curve is sigmoid because binding of oxygen to one haem raises the affinity of the others (cooperativity). The flat upper part protects loading when alveolar oxygen falls a little; the steep part lets tissues unload large amounts for a small fall in partial pressure. The P50, the partial pressure at 50 per cent saturation, describes affinity. The curve shifts right (lower affinity, easier unloading) with higher carbon dioxide, hydrogen ions (the Bohr effect), temperature and 2,3-diphosphoglycerate. Species differ: red cells of dogs, horses and pigs contain much 2,3-DPG, whereas those of cats and ruminants contain little, and their haemoglobin instead has a low intrinsic affinity for oxygen. Fetal haemoglobin, or fetal red cells, have higher affinity than maternal blood, favouring transfer across the placenta.
Carbon dioxide is carried in three forms: as bicarbonate (the majority, roughly 70 per cent in most textbooks), bound to amino groups on haemoglobin as carbamino compounds (roughly 20 per cent) and dissolved (roughly 10 per cent). In red cells carbonic anhydrase catalyses the hydration of carbon dioxide to carbonic acid, which dissociates to hydrogen ions, buffered by haemoglobin, and bicarbonate, which leaves the cell in exchange for chloride through band 3, the chloride shift. Deoxygenated haemoglobin binds hydrogen ions and carbon dioxide more readily than oxyhaemoglobin, so unloading oxygen in the tissues helps blood pick up carbon dioxide, and loading oxygen in the lung helps release it: this is the Haldane effect. Oxygen extraction by the tissues is the arteriovenous content difference divided by arterial content, commonly about a quarter at rest.
Hypoxia means inadequate oxygen at tissue level and is classed by cause. Hypoxaemic hypoxia is low arterial oxygen partial pressure: high altitude, hypoventilation, ventilation-perfusion mismatch, shunt or diffusion impairment. Anaemic hypoxia is low oxygen content with normal partial pressure: anaemia, carbon monoxide or methaemoglobin. Stagnant or circulatory hypoxia is inadequate flow: shock, heart failure or thrombosis. Histotoxic hypoxia is failure of the cell to use oxygen, as in cyanide poisoning, which blocks cytochrome oxidase and leaves venous blood bright red. Carbon monoxide binds haemoglobin with far greater affinity than oxygen and shifts the remaining curve to the left, so blood is cherry red and PaO2 may be normal. Nitrate, reduced to nitrite in the rumen, oxidises haemoglobin iron to the ferric state, producing methaemoglobin, which cannot carry oxygen, so the blood is chocolate brown; ruminants are the classic victims when they eat nitrate-accumulating forage. Paracetamol (acetaminophen) causes methaemoglobinaemia and Heinz body anaemia in cats, whose haemoglobin is especially prone to oxidation.
The fraction of oxygen in air is the same at every altitude, about 21 per cent, but barometric pressure falls with height, so the partial pressure of inspired oxygen falls. Water vapour pressure at body temperature does not change, so it takes a larger share of the available pressure. With a barometric pressure of 523 mmHg, a value reached somewhere around 3,000 metres, inspired oxygen is 0.21 times (523 minus 47), about 100 mmHg, and if PaCO2 stayed at 40 mmHg alveolar oxygen would be only about 50 mmHg, on the steep part of the dissociation curve. The animal's first line of defence is to breathe more. Hyperventilation lowers PaCO2; at a PaCO2 of 30 mmHg, the same air gives an alveolar oxygen of about 62 mmHg. Acclimatisation is the set of changes in an individual over days to weeks. Ventilation rises further over the first days as the central chemoreceptors adapt: hyperventilation causes respiratory alkalosis, the choroid plexus and the kidney remove bicarbonate (the kidney excretes it in the urine), pH comes back towards normal and the brake on breathing is released. Hypoxia stimulates renal erythropoietin through hypoxia-inducible factor, so haemoglobin and haematocrit rise over weeks; too much polycythaemia raises blood viscosity. In species whose red cells have 2,3-DPG, its concentration rises and shifts the curve to the right, which helps unloading, although at severe altitude a left shift from alkalosis helps loading in the lung. The pulmonary vessels constrict in response to alveolar hypoxia everywhere in the lung at once, so pulmonary arterial pressure rises.
Cattle are especially susceptible to hypoxic pulmonary hypertension because their small pulmonary arteries have a thick muscular media and constrict strongly to hypoxia, and their lungs have little collateral ventilation. At high altitude, commonly above about 1,500 to 2,000 metres, some cattle develop high mountain disease, or brisket disease: sustained pulmonary hypertension leads to right ventricular hypertrophy and then congestive right heart failure, with subcutaneous oedema of the brisket and ventral neck, jugular distension, ascites and hydrothorax. Susceptibility is heritable, so pulmonary arterial pressure is measured by catheter in bulls intended for high-altitude herds; the cut-offs used vary with the altitude of testing, the age of the animal and the breed association. Pigs also show strong hypoxic pulmonary vasoconstriction. Fast-growing meat-type chickens develop pulmonary hypertension syndrome, better known as ascites syndrome, when their oxygen demand outstrips a relatively small, rigid lung; altitude, cold and poor ventilation all worsen it, and right ventricular failure fills the abdomen with fluid. Native high-altitude animals have genetic adaptations rather than just acclimatisation. South American camelids (llama, alpaca, vicuna) have haemoglobin with a high oxygen affinity, a left-shifted curve that favours loading in the lung, together with small oval red cells, and they do not become as polycythaemic as lowland animals taken to altitude. The yak has thin-walled pulmonary arteries and little hypoxic pulmonary vasoconstriction, so it does not develop the pulmonary hypertension that affects lowland cattle at the same altitude. Bar-headed geese, which fly over the Himalaya, have haemoglobin with high oxygen affinity and the efficient avian lung. The general lesson for the examiner is that a left-shifted curve helps when loading is the limiting step (very low inspired oxygen), whereas a right-shifted curve helps when unloading is limiting (exercise at sea level).
The kidney's working unit is the nephron: a glomerulus within Bowman's capsule, then the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule and the collecting duct. Cortical nephrons have short loops; juxtamedullary nephrons have long loops that dip deep into the medulla and build the concentration gradient. Cattle kidneys are externally lobulated; the pig's are smooth but multipapillary; the dog, cat, sheep, goat and horse have a single fused renal crest. The kidneys receive about a fifth to a quarter of cardiac output. The juxtaglomerular apparatus, where the distal tubule touches its own glomerulus, contains the macula densa, which senses sodium chloride delivery, and the renin-secreting granular cells. Filtration across the glomerular barrier (fenestrated endothelium, basement membrane and podocyte slit diaphragms) is driven by glomerular capillary hydrostatic pressure, opposed by hydrostatic pressure in Bowman's space and by plasma oncotic pressure. The barrier restricts molecules by size and by negative charge, so albumin is largely held back; protein in the urine is an early sign of glomerular disease. The glomerular filtration rate (GFR) is controlled mainly by the tone of the afferent and efferent arterioles: constricting the afferent arteriole lowers GFR, while moderate constriction of the efferent arteriole raises glomerular pressure and GFR. Autoregulation holds renal blood flow and GFR nearly constant over a wide range of arterial pressure through the myogenic response and tubuloglomerular feedback: when the macula densa senses more sodium chloride, the afferent arteriole constricts. Below the autoregulatory range, as in shock or under deep anaesthesia, GFR falls with pressure, which is why anaesthetised patients' blood pressure is supported and why non-steroidal anti-inflammatory drugs, which remove prostaglandin-mediated afferent dilation, are risky in dehydrated animals.
Clearance is the volume of plasma completely cleared of a substance per minute: urine concentration times urine flow divided by plasma concentration. A substance that is freely filtered and neither reabsorbed, secreted nor metabolised has a clearance equal to GFR; inulin is the classical marker, and iohexol plasma clearance is used clinically. Creatinine, made at a steady rate from muscle, approximates GFR, which is why serum creatinine rises as GFR falls, though only after a large part of function is lost, and why muscle mass affects it; symmetric dimethylarginine is an alternative marker. Para-aminohippuric acid (PAH) is filtered and almost completely secreted at low plasma levels, so its clearance estimates renal plasma flow; renal blood flow is plasma flow divided by (1 minus haematocrit). The filtration fraction is GFR divided by renal plasma flow, commonly about a fifth. If a substance's clearance is less than GFR it is net reabsorbed; greater than GFR, net secreted. The filtered load is GFR times plasma concentration. Glucose is reabsorbed by carriers with a transport maximum, so once the filtered load exceeds that maximum glucose appears in the urine. The plasma level at which this starts, the renal threshold, differs by species: it is low in cattle, so excitement hyperglycaemia readily causes glucosuria, and higher in cats than in dogs, although the marked stress hyperglycaemia of cats can still exceed it.
The proximal tubule reabsorbs about two-thirds of filtered sodium and water isosmotically, nearly all filtered glucose and amino acids, and most bicarbonate, phosphate and potassium, and it secretes organic acids and bases, including many drugs. The thick ascending limb of Henle reabsorbs sodium, potassium and chloride through the NKCC2 cotransporter, the target of loop diuretics such as furosemide, while being impermeable to water, so it dilutes the tubular fluid and builds the medullary gradient. The distal convoluted tubule reabsorbs sodium chloride through a thiazide-sensitive cotransporter and is a site of calcium reabsorption under parathyroid hormone. In the collecting duct principal cells reabsorb sodium through epithelial sodium channels and secrete potassium under aldosterone, and let water through aquaporin-2 channels under antidiuretic hormone; intercalated cells secrete hydrogen ions or bicarbonate. Ruminants recycle urea: much of the urea made in the liver returns to the rumen in saliva and across the rumen wall and is used by microbes for protein synthesis, and on low-protein diets the kidney excretes a smaller fraction of filtered urea. Herbivore urine is usually alkaline; horse urine is normally cloudy and viscous with mucus and calcium carbonate crystals. Birds excrete most of their nitrogen as uric acid, which is made in the liver, secreted by the proximal tubules and passed as a colloidal suspension that needs little water. The avian kidney has two kinds of nephron: small reptilian-type nephrons without loops of Henle, which are the majority, and mammalian-type nephrons with loops arranged in medullary cones, so birds can concentrate urine only modestly, to about twice plasma osmolality. Birds have a renal portal system in which blood from the hind limbs can pass to the peritubular capillaries, and they have no urinary bladder: urine enters the cloaca and is moved back into the coprodeum and colon, where water and salt are reabsorbed.
Osmolality is the number of osmotically active particles per kilogram of water; plasma osmolality in mammals is commonly around 290 to 310 mOsm/kg, with species and laboratory differences. Sodium and its anions account for most of it, so plasma osmolality can be estimated as twice the sum of sodium and potassium plus glucose plus urea, all in mmol/L; with glucose and urea in mg/dL, glucose is divided by 18 and blood urea nitrogen by 2.8. With sodium 145, potassium 4, glucose 90 mg/dL and urea nitrogen 14 mg/dL the estimate is 308 mOsm/kg. The measured value minus the calculated value is the osmolal gap; a large gap means an unmeasured osmole, classically ethylene glycol early after ingestion. Tonicity is the part of osmolality that moves water across cell membranes: urea crosses membranes and adds to osmolality but not to effective tonicity, whereas sodium and glucose (in the absence of insulin) are effective osmoles. Urine concentration in the clinic is estimated by refractometric specific gravity. Urine with a specific gravity of about 1.008 to 1.012 has the same osmolality as plasma (isosthenuria); below that it is dilute (hyposthenuria), which requires working tubules; above it the kidney is concentrating. The level of concentration regarded as adequate differs by species and by text, being higher for cats than for dogs, horses and cattle.
Antidiuretic hormone (arginine vasopressin in most mammals; lysine vasopressin in pigs; arginine vasotocin in birds) is made in the supraoptic and paraventricular nuclei of the hypothalamus and released from the posterior pituitary. Osmoreceptors near the third ventricle trigger its release when plasma osmolality rises by a few per cent; large falls in blood volume or pressure also release it and can override osmotic control. It acts on V2 receptors in collecting duct principal cells, raising cyclic AMP and inserting aquaporin-2 into the luminal membrane; water then leaves the duct into the hypertonic medullary interstitium. That interstitium is made hypertonic by the countercurrent multiplier: the thick ascending limb pumps salt out without water, the descending limb loses water to the concentrated interstitium, and the hairpin flow multiplies a small transverse gradient into a large gradient from cortex to papilla. Urea recycling from the inner medullary collecting duct adds to it, and the vasa recta, as countercurrent exchangers, remove water without washing the gradient away.
Water intake is driven by thirst, stimulated by raised osmolality, by volume depletion and by angiotensin II. Diabetes insipidus is polyuria with dilute urine: central when antidiuretic hormone is not made, nephrogenic when the kidney does not respond. A modified water deprivation test, followed by a test dose of the hormone, separates the two from primary (psychogenic) polydipsia, but it must be supervised because it can dangerously dehydrate an animal that cannot concentrate. Salt poisoning, or water deprivation followed by unrestricted access to water, is classic in pigs and also occurs in cattle and poultry: brain cells that have adapted to high sodium by accumulating osmolytes swell when water returns, causing cerebral oedema and nervous signs. The same principle means chronic hypernatraemia or hyponatraemia must be corrected slowly. Water intoxication after rapid intake of large volumes by thirsty calves causes intravascular haemolysis and haemoglobinuria.
The kidney's handling of water can be split into osmolar clearance, the plasma volume that would carry the excreted solutes at plasma osmolality (urine osmolality times urine flow divided by plasma osmolality), and free water clearance, which is urine flow minus osmolar clearance. Positive free water clearance means dilute urine, water being excreted in excess of solute; negative means concentrated urine. With urine flow 2 mL/min, urine osmolality 150 and plasma osmolality 300 mOsm/kg, osmolar clearance is 1 mL/min and free water clearance is +1 mL/min. Desert-adapted species show what the system can do. The camel tolerates large water losses, can let its body temperature rise by day and lose the stored heat at night, sheds water mainly from interstitial and intracellular fluid while protecting plasma volume, has red cells that resist osmotic lysis when it drinks a large volume quickly, and produces concentrated urine.
Arterial pH is normally held within a narrow range close to 7.4 in mammals, although reference intervals differ by species, sample site and laboratory. pH is the negative logarithm of hydrogen ion concentration: pH 7.40 is about 40 nanomoles per litre and pH 7.10 about 80, so a fall of 0.3 units doubles the hydrogen ion concentration. The body defends pH with buffers, then with the lungs (minutes) and then with the kidneys (hours to days). The main extracellular buffer is bicarbonate-carbonic acid, powerful because it is an open system: carbon dioxide is removed by the lungs and bicarbonate adjusted by the kidneys. Haemoglobin is the main blood non-bicarbonate buffer, and phosphate and proteins buffer inside cells and in urine. The Henderson-Hasselbalch equation for the bicarbonate system is pH = 6.1 + log (bicarbonate / (0.03 x PCO2)), with bicarbonate in mmol/L and PCO2 in mmHg. With bicarbonate 24 and PCO2 40 the ratio is 20 and pH is 7.40. The equation shows that pH depends on the ratio, not on either value alone: the kidneys control the numerator and the lungs the denominator.
A metabolic acidosis is a primary fall in bicarbonate (or a fall in strong ion difference): diarrhoea with bicarbonate loss, lactic acidosis in shock or grain overload, ketoacidosis, renal failure, and ethylene glycol. The lungs compensate by hyperventilating to lower PCO2. A metabolic alkalosis is a primary rise in bicarbonate, usually from loss of chloride-rich gastric or abomasal fluid; the lungs compensate by hypoventilating, within limits set by hypoxaemia. A respiratory acidosis is a primary rise in PCO2 from hypoventilation: anaesthesia, airway obstruction, neuromuscular weakness, severe lung disease; the kidneys compensate by retaining bicarbonate and excreting acid as ammonium, which takes days. A respiratory alkalosis is a primary fall in PCO2 from hyperventilation: panting in heat stress, pain, hypoxaemia and altitude; the kidneys excrete bicarbonate. Compensation moves pH back towards normal but rarely reaches it and never overshoots, so a normal pH with abnormal bicarbonate and PCO2 suggests a mixed disorder. The expected compensation for each disorder is published as species-specific rules of thumb, which differ between texts; use the one for the species you are treating. The renal part rests on reabsorbing filtered bicarbonate (mostly proximal), generating new bicarbonate by excreting titratable acid (mainly phosphate) and ammonium made from glutamine.
The anion gap is the difference between the main measured cations and anions: (sodium plus potassium) minus (chloride plus bicarbonate), or the same without potassium; reference intervals depend on which formula the laboratory uses. It reflects unmeasured anions, mostly albumin and phosphate. A metabolic acidosis with a raised anion gap means an acid with an unmeasured anion has been added: lactate, ketones, uraemic anions, or glycolate and oxalate from ethylene glycol. A metabolic acidosis with a normal gap is hyperchloraemic, as with bicarbonate loss in diarrhoea or excessive saline. Because albumin is the main unmeasured anion, hypoalbuminaemia lowers the gap and can hide a lactic acidosis. The physicochemical (Stewart) approach, widely used in large-animal medicine, says that pH is determined by three independent variables: PCO2, the strong ion difference (mainly sodium plus potassium minus chloride and lactate), and the total concentration of weak non-volatile acids (albumin, globulin and phosphate). Bicarbonate is a dependent variable. A fall in strong ion difference, from hyperchloraemia, hyponatraemia or lactate, causes acidosis; a rise, from hypochloraemia, causes alkalosis; a rise in albumin or phosphate causes acidosis.
Several acid-base disorders are classic in ruminants. Left or right displacement or volvulus of the abomasum, and other forms of abomasal outflow obstruction such as vagal indigestion, trap hydrochloric acid in the abomasum and cause reflux into the rumen, giving hypochloraemic, hypokalaemic metabolic alkalosis. When chloride and volume are depleted the kidney keeps reabsorbing sodium and bicarbonate and secretes hydrogen ions, so the urine is acidic despite the alkalaemia: paradoxical aciduria. Treatment centres on chloride and potassium replacement. Grain overload causes rumen lactic acidosis, with a fall in rumen pH, absorption of D- and L-lactate and systemic metabolic acidosis with a high anion gap. Neonatal calves with diarrhoea develop metabolic acidosis from faecal bicarbonate and sodium loss and from D-lactate produced by colonic fermentation; the D-lactate contributes to their depression and weakness. The base deficit is sometimes used to estimate the bicarbonate needed: body weight in kilograms times the base deficit times a distribution factor, commonly taught as 0.3 in adults and higher in neonatal calves, but the factor differs by text and the calculated amount is usually given in part and reassessed. Pyloric obstruction in a vomiting dog causes the same hypochloraemic alkalosis as abomasal disease in the cow. Hens panting in hot weather lose carbon dioxide, become alkalotic and have less bicarbonate available for shell formation, so eggshells become thin.
Use this subject to build the equations you will use for the rest of your career: cardiac output, the Fick principle, clearance, red cell indices, the alveolar gas equation and Henderson-Hasselbalch. Work each by hand until the units come out right. Learn the species differences as pairs: the horse has no circulating reticulocytes and a deep-Purkinje ECG; the cat and ruminant have little 2,3-DPG; the bird has air sacs and uric acid. When you read a clinical case later, you should be able to say which controlled variable has moved and which reflex is trying to bring it back.
In practice this subject is what you use when you decide how much fluid to give a scouring calf, read a coagulation panel from a dog that ate rat bait, judge whether a cat's urine specific gravity is adequate before anaesthesia, or explain why a horse's PCV rose when it was frightened. It tells you why an abomasal displacement cow needs chloride and potassium rather than bicarbonate, why a panting heat-stressed herd has alkalotic blood, and why an anaesthetised horse on oxygen can still be hypoxaemic. Always use your own laboratory's reference intervals for the species in front of you.
After decades in practice or herd health, the value of physiology is in systems thinking: the link between altitude, genetics and brisket disease when choosing bulls for a hill herd; heat stress, panting and eggshell quality in a layer unit; water supply and salt poisoning risk in a pig farm; and the balance of fluid, acid-base and electrolytes in hospital protocols. Senior clinicians use it to audit protocols, train juniors to reason from mechanism rather than memory, and to spot when a textbook rule of thumb derived in one species is being misapplied to another.
A researcher uses this subject as the frame for questions still open: the genetics of hypoxic pulmonary vasoconstriction in cattle and yaks, the strong ion model applied to neonatal calf diarrhoea and D-lactate, avian cross-current gas exchange and renal portal flow, the control of urea recycling in ruminants on low-protein diets, and species differences in haemoglobin oxygen affinity. Designing such work needs careful measurement (indicator dilution, clearance, blood gases handled anaerobically), species-appropriate reference data, and awareness that many classic numbers came from a small number of animals and breeds.
This manual does not give species reference intervals for haematology, blood gases, electrolytes or urine specific gravity as tables; values differ by laboratory, analyser, breed and age, and the reader must use the local laboratory's intervals. It does not give species-specific expected-compensation formulas for acid-base disorders, maintenance fluid rates or bicarbonate dosing, which belong to clinical texts and differ between them. Exact pulmonary arterial pressure cut-offs for bull selection, precise erythrocyte life spans and P50 values for each species are omitted or given only approximately. Fish, reptile and laboratory-animal physiology, exercise physiology, fetal and neonatal circulation in depth, and lymphatic physiology are covered only in passing. Digestion, muscle, nerve, endocrine and reproductive physiology are in Veterinary Physiology II.
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