Water
● TBW: 60 - 70% (Up to 90%) in neonates
○ ICF (67%)
○ ECF: Interstitial (25%) and Plasma (8%)
● Affects TBW
○ Body fat
○ Activity or purpose
○ Stage of growth
■ ECF volume: adult levels by 6
months of age
Sources of Water
● Drinking Water
○ Species, breed, age, and physiologic
factors affects volume of water
requirements
○ Increased environmental
temperature increases water needs
● Feed – Water content affects water intake
● Metabolic water – Produced during the
catabolism of biomolecules to CO2 and H2O
via hydrolysis or oxidation
○ Affected by feed composition
■ High fat and protein diets
increase water intake due to
increased metabolic waste,
urinary excretion of urea and
heat produced in metabolism
○ Glucose > Protein > FA
○ Water deprivation increases food
intake to oxidize more macronutrients
■ Lipids are oxidized first
■ Prolonged water deprivation
leads to switch to
carbohydrate oxidation to
enhance metabolic water
production and minimize
respiratory water loss
Functions of Water
● Hydrolysis and Energy Production
● Digestion: Ingested as drink or as moisture
content in feeds
○ Activates sodium bicarbonate layer to
protect stomach against HCl
○ Saliva and mucus lining: mostly water
○ Ruminants chew their food for several
hours
■ Saliva adds to the volume of
ruminal or stomach fluids to
regulate pH of stomach
● pH regulation: Acts as acid or base when it
ionizes
● Joint Lubrication: Major component of
synovial or joint fluid; can be used to diagnose
different joint pathologies
○ Articular cartilage – provides
lubrication and prevents wear
● Temperature Regulation – acts as a buffer
against overheating due to its high specific
heat
○ Specific heat - how much heat an
object can absorb without increasing
its own temperature
Properties of Water
● Large heat capacity, large capacity for
vaportization
● Electronegativity – measures the affinity of
an atom’s nucleus for its outer electrons
● Polarity
○ Its partial separation charge allows
for a dipole moment, which allows
each water molecule to form H bonds
with other molecules
■ Adhesion and cohesion
■ Capillary action
○ H bonds stabilize complex protein
structures and DNA
● Universal solvent – uses its partial charge to
dissolve compounds
○ Miscibility – occurs between two
liquids of similar polarity
○ Amphiphilic – intermediate level of
solubility
○ Hydrophobic effect – the chemical
property of non-polar parts of a
molecule to associate with each other
to the exclusion of water
■ Liposome
■ Micelle
■ Bilayer sheet
● Ionization – can act as a weak acid or base
Potential or Power of Hydrogen (pH)
● Negative logarithm of the proton
concentration
● Change of 1 ph unit = tenfold increase in
proton concentration
Importance of pH in Animals
● pH of our blood: 7.35 to 745
○ pH of < 6.8 or > 7.8: bonds of critical
proteins will be destroyed → results in
death
● Intracellular pH: 6.0 to 7.4
 ○ Extreme alterations in extracellular pH
can disrupt integrity of the
intracellular environment → interfere
with metabolism
Acid-Base Physiology
● The ph balance of the body is achieved
through the coordinated activities of the
lungs, liver, and kidneys
○ Net H+ production = Net H+ excretion
● Dietary intake and metabolism of
macronutrients are sources of both acids and
alkali
○ Volatile acid (~7,000 mEq/day) (CO2)
eliminated by the acids
○ Non-volatile acid (H+) (~30 mEq/day)
is excreted in urine
● Hydrogen Ion Concentration
○ In ECF, it's maintained within narrow
limits: normally ~40 nmol/L
○ One-millionth the concentration of
other common electrolytes
○ Have profound effects on metabolic
events, largely through interaction
with cellular proteins
○ Interactions alter protein
configuration, which alter function
Systems that Regulate pH
● Extracellular and Intracellular Buffer System
○ Only takes seconds
○ Extracellular buffers: Bicarbonate
and phosphate buffer pairs, plasma
proteins
○ Intracellular buffers: Protein, organic
and inorganic phosphates,
hemoglobin (in RBC)
○ Bone – source of carbonate;
contributes up to 40% of buffering
capacity when there’s acute acid
load
● Respiratory System
○ Ventilatory control of plasma CO2
○ Takes 2-3 minutes
○ Lungs function in ventilation by
removing pCO2 (and therefore H2CO3)
from the blood
■ High blood CO2 - increase in
respiration
■ Low blood CO2 - decrease in
respiration
● Urinary System
○ Urinary excretion of bicarbonate or an
acid urine
○ Strongest but slowest effect (hours to
days)
■ 2 - 5 days for maximum effect
○ Regulate bicarbonate blood levels
through renal absorption and/or
excretion of hydrogen ions as acidic
urine
○ Excreted urine: acidic or alkaline need
to readjust ECF [H+] toward normal
Carbonic acid-Bicarboante Buffer System
● CO2 + H2O* ⇌ H2CO3 ⇌ H+ + HCO3-
○ *Carbonic anhydrase: abundant in
lung alveoli walls and epithelial cells
of the renal tubules
● Regulated by respiratory (carbonic acid
concentration) and urinary (bicarbonate
concentration) system
● Only one measured for calculation of
acid-base status of patients
● Most commonly evaluated buffer system
○ Bicarbonate is found in relatively high
concentrations in the body
○ Relatively easy to measure
○ The buffer system over which the
body has the biggest control
● Mechanism in the respiratory system (CO2 +
H2O* ⇌ H2CO3)
○ Venous blood entering the lungs has
more carbonic acid
○ Carbonic anhydrase reverses the
reaction to produce CO2 and H2O
○ Exhalation lowers [CO2] and [H2O]
○ Oxygenated blood has lowered
carbonic acid concentration
● Mechanism in the urinary system (H2CO3 ⇌ H+
+ HCO3-)
○ Only certain parts are involved in the
reabsorption and excretion of the ions
involved in this buffer system
○ Hydrogen is released in the urine and
the bicarbonate is reabsorbed in the
blood stream and the kidneys
Phosphate Buffer System
● H2PO4 ⇌ H+ + HPO4-
● Plays a major role in buffering the renal
tubular fluids and intracellular fluids, but not in
the ECF
○ Phosphate is greatly concentrated in
the kidney tubules
○ The tubular fluid in the kidney has a
considerably lower pH than the ECF,
 bringing the operating range of the lumen where it combines with
buffer closer to pKa 6.8 of the system ammonia to form
○ The concentration of phosphate in the ammonium, and it is secreted
ICF is many times higher than that of into the urine while
the ECF, and the ICF pH is usually bicarbonate ions are
closer to the pKa of the phosphate reabsorbed into the blood
buffer system compared to the ECF stream
● Doesn't play a major role in maintaining blood ■ For each ammonium
pH because it has very low concentration in secreted, a new bicarbonate
the extracellular fluids is generated and added to
● Majority of phosphate is eliminated in urine the blood
● Includes both organic and inorganic ● Hemoglobin
phosphates, concentrations are too low ○ H2CO3 + Hb- ⇌ HHb + HCO3-
● pH range = 7.2 (pKa) ± 1 ○ Binds with the small amounts of acid
● Mechanism in the blood before it can alter the pH
○ Hydrogen ion secreted into the ○ Happens with the erythrocytes
tubular lumen combines with a ○ The input of CO2 in the erythrocyte
phosphate buffer to form dihydrogen causes an increase in hydrogen
phosphate, and bicarbonate ions are formation
reabsorbed into the blood ○ It is believed that the free-carboxyl
○ Since hydrogen binds with a buffer and amino groups of the hemoglobin
other bicarbonate, there is a net gain provide little buffering, and it is the
of bicarbonate by the blood imidazole group of the 38 histidine
residues of hemoglobin that are the
Protein Buffer System important buffer
● Can occur both in the ICF and ECF ○ Mechanism
● Ammonium-Ammonia ■ In the erythrocytes, carbon
○ NH3 + H+ ⇌ NH4+ dioxide is rapidly converted to
○ Largely comes from the deamination carbonic acid by carbonic
of glutamine and amino acid from the anhydrase, and most (80%) of
kidneys, where it is pronated to the it ionizes into hydrogen and
ammonium ion bicarbonate ion. Hemoglobin
○ pKa = 9.0 combines with hydrogen
○ NH3:NH4+ is ~1:100 at pH 7.0 while the bicarbonate ion is
○ Protonated NH4+ does not cross the transported out of the
blood brain barrier (BBB) easily erythrocyte
○ Alkalemia: increase in free NH3 ■ The remaining carbon dioxide
uptake into CNS leads to coma can bind non-enzymatically
○ Loop diuretic overuse: increased NH3 to the amine terminal of the
uptake into CNS leads to hypokalemia globin peptide of the
and metabolic alkalosis ensue hemoglobin, forming
○ Mechanism carbaminohemoglobin
■ Upon metabolism in the
proximal tubular cells of the Acidosis and Alkalosis
kidney, glutamine produces ● Metabolic Acidosis (↑ H+, ↓↓ HCO3-, ↓ pCO2)
two ammonium ions and two ○ Primary deficit of bicarbonate ions in
bicarbonate ions the blood
■ The ammonium ion is ○ {HCO3-] loss
secreted into the tubular ■ Diarrhea (loss of alkaline
lumen in exchange for fluids in the GIT)
sodium ○ [H+] addition (↑ formation or
■ In the collecting tubules, ingestion of acids)
hydrogen is secreted by the ○ [H+] removal
tubular membrane into the
 ■ ↑ uric acid - kidney disease or ■ Diuretic usage — increases
renal failure because H ions water secretion
are not excreted ○ Contraction alkalosis
○ Compensatory Mechanism: ■ ↓ ECF volume loss or
Hyperventilation to remove CO2 sequestration of Na and Cl
■ Urinary excretion of NH4Cl without enough HCO3- loss
and monobasic phosphate - ○ Compensatory Mechanism:
voiding of acidic urine Hypoventilation to increase CO2
● Respiratory Acidosis (↑ H+, ↑↑ pCO2, ↑HCO3-) retention
○ Abnormal retention or high levels of ■ Urinary excretion of HCO3 ions
CO2 in the blood due to hypercapnea - voiding of alkaline urine
(high pCO2) or improper elimination ● Respiratory Alkalosis (↓ H+, ↓↓ pCO2, ↓
of CO2, leading to accumulation of H+ HCO3-)
ions ○ Deficit of CO2 in the blood
○ Increase in reabsorption of (hypocapnea)
bicarbonate ions in the renal system ○ Increase in reabsorption of
○ ↓ CO2 removal - Hypoventilation bicarbonate ions in the renal system
■ Respiratory center depression or increase in urine output of
■ Neuromuscular disease bicarbonate ions by the kidneys
■ Restrictive extrapulmonary ○ Hyperventilation due to hypoxemia
disease ■ Pulmonary disease
■ Intrinsic pulmonary and small ■ Congestive heart failure
airway disease - pneumonia, ■ Severe anemia
pulmonary fibrosis, and ○ Medullary respiratory center
edema stimulation
■ Large airway obstruction - ■ Salicylate intoxication
obstruction of trachea and ■ Encephalitis
larynx ■ Brain tumor
○ ↑ CO2 production ○ Evaporative processes
■ Malignant hyperthermia ■ Prevent overheating
■ Cardiac arrest in some cases ○ Psychogenic disturbances
○ Compensatory Mechanism: Metabolic ■ Pain, fear, anxiety
■ ↑ formation of HCO3- by ○ Compensatory mechanism:
kidney tubular cells Metabolic
■ Renal excretion of H+ ions as ■ Urinary excretion of HCO3 ions
NH4+ ● Respiratory + Metabolic Disorder
■ Buffering blood pH ions with ○ Dog in shock with thoracic injury
hemoglobin ● Combination of 2 Metabolic Disorder
● Metabolic Alkalosis (↓ H+, ↑↑ HCO3-, ↑ pCO2) ○ Dehydrated and vomiting animal
○ Primary excess of HCO3- ions in the
blood Heat
○ [HCO3-] addition ● Definition: The total energy of the molecular
■ Ingestion of alkaline salts of motion inside that object
organic acids (NH4Cl) ● SI Unit: Joule
○ ↑ [H+] removal ● Units: Joules, Calories
■ Gastric vomiting (loss of HCl) ● Depends on the factors, such as speed, size,
■ Abomasal reflux of HCl into and number of particles
the rumen
■ ↑ renal excretion of H ions Temperature
● Excess aldosterone ● Definition: Measure of the thermal energy or
(mineralcorticoid) average heat of the molecules in a substance
secretion or ● SI Unit: Kelvin
hyperaldosteronism ● Units: Fahrenheit, Celsius, Kelvin
 ● If heat is added or removed, temperature
goes up and down depending on its specific
heat capacity, which is related to density
Effect of Temperature on Cells
● Cells function best at normal physiological
temperature (37C for most mammals)
● Fluid State of Membrane
○ High temperatures: Increased
membrane fluidity and permeability
○ Very low temperatures: Decreased
membrane fluidity and permeability
■ In prolonged exposure to
subfreezing temperature,
liquid in the cell could also
freeze, forming crystals that
pierce the membrane and
might ultimately kill the cell
● Enzyme Activity
○ Affected by abnormally high
temperature, resulting in denaturation
○ Their optimal rate of activity is at a
narrow temperature range
● Protein Synthesis
○ At elevated temperature, forces
between charged groups disrupt the
bonds between non-polar groups of
proteins, affecting its higher structure
and function
○ Integral and peripheral proteins in the
cell membrane function as
transporters and receptors are
affected by temperature
○ At physiological temperature, cells
protein translation from RNA occur at
a normal phase without the help of
heat or cold shock proteins
■ Proteins that help in the
folding of the proteins
Pathways of Heat Gain and Loss
● Body heat = heat produced (within the
animal) + heat gained (from the
environment) - heat lost (to the environment)
● TOTAL = MET + COND + CONV + RAD + EVAP
Metabolic Heat Production
● Heat metabolism - produced by metabolic
reactions
● Energy transformation that’s not perfect in the
body → some of the energy is lost in the form
of heat
Classification of Animals' Body Temperatures
● Endotherms - animals that can produced
heat endogenously or within themselves and
can regulate their own body temperature
through metabolic processes
● Ectotherms – animals that can’t produce
their own heat, so they rely on ambient
temperature by moving to environments with
favorable temperatures
● Homeotherms – animals that maintain body
temperature at a constant temperature
● Poikilotherms – animals with variable body
temperature due to variation in ambient
temperature
● Most domestic animals are endotherms and
homeotherms
○ Function best at a specific
temperature range called the
thermoneutral zone
■ A range of temperatures
within which the metabolic
heat production is unaffected
by temperature change and
maintain constant body
temperature
■ Heat lost = heat gained
● Lower critical temperature (cold stress) –
hypothermia
● Upper critical temperature (heat stress) –
hyperthermia
Hydroregulation and Thermoregulation
● Hydroregulation – the set of behavioral and
physiological mechanisms to control water
balance and remain hydrated
● Major Mechanisms
○ Water conservation processes
○ Through physiological and behavioral
changes, as well as the production
and regulation of urine and feces
○ Mechanisms to regulate water intake
through habitat selection and
drinking behavior
○ Foraging behavior and metabolic
water production
● Physiological Changes
○ Water evaporation
■ Cold-defense: Inhibited
■ Heat-defense: Sweating,
panting, saliva spreading
○ Skin blood flow
■ Cold-defense:
Vasoconstriction
■ Heat-defense: Vasodilation
 ○ Shivering thermogenesis
■ Cold-defense: Activated
■ Heat-defense: Inhibited
○ Non-shivering (BAT) thermogenesis
■ Cold-defense: Activated
■ Heat-defense: Inhibited
● Behavioral Changes
○ Postural changes
■ Cold-defense: Reduced
exposed surface
■ Heat-defense: Increased
exposed surface
○ Temperature choice
■ Cold-defense: Heat-seeking
■ Heat-defense: Cold-seeking
○ Altering microenvironment
■ Cold-defense: Nesting, social
huddling
■ Heat-defense: Air
conditioning
● Water intake
○ Animals that feel cold drink less and
feed more
○ Animals that feel hot drink more and
feed less
Protein Sources
● Exogenous dietary proteins – absorbed as
amino acids and peptides in the small
intestine
● Endogenous or de novo amino acid
synthesis – new amino acids synthesized
from carbon skeletons and alpha amino
groups of other amino acids
○ Transcription of DNA to RNA and
translation of RNA to polypeptides to
synthesize proteins is also possible
● Protein turnover – amino acids are derived
from the breakdown of cellular and tissue
proteins for the synthesis of new proteins
Protein Denaturation
● Folding or coiling of proteins are dissolved,
and only a single polypeptide strand can be
seen
● The stomach has a highly acidic pH of around
2 (ranges from 1.5 to 12.5 in some mammals)
because of the HCl secretion from the fundic
parietal cells
● The chief cells in the stomach secretes
pepsinogen I and II, which is activated by
acidic pH (1.8 to 3.5) into pepsin
● In young ruminants, the renin, also known as
chymosin, is present in the abomasum
○ A hydrolase that catalyzes the
cleavage of kappa casein chain to
form soluble paracasein, which then
reacts to calcium to form a curd
● Pepsin and renin: endopeptidases that
cleave peptide bonds on the carboxyl side of
aromatic and acidic amino acids
○ Also for leucine and methionine
● The acidic chyme is neutralized when mixed
with the alkaline bile and pancreatic juice in
the duodenum
Peptide Bond Cleavage
● Chyme stimulates the release of
cholecystokinin in the duodenum and
activates the pancreas
○ Cholecystokinin: a hormone that
stimulates gall bladder contraction
and acinar pancreatic enzyme
secretion
● The proximal small intestine has a borderline
acidic pH of 6 due to pancreatic bicarbonate
secretions
● Protein digestion and amino acid absorption
starts at the duodenum, but occurs mostly in
the jejunum
● Luminal digestion of proteins results in small
and large peptides and free amino acids,
brought about by pancreatic proteases and
peptidases
● Most enzymes are from the pancreas and
secreted in active form
● Proteases – a subset of hydrolyses that
specifically hydrolyze peptide bonds and are
able to separate one amino acid from
another amino acid
○ Exopeptidase – act on the terminals
(aminopeptidase, carboxypeptidase)
○ Endopeptidase – act on interior
peptide bond
● Trypsinogen is activated by enterokinase
into trypsin by cleaving a hexapeptide from
its end terminal
○ Enterokinase: an enteropeptidase on
the duodenal brush border
○ Trypsin: an endopeptidase with a
positive feedback mechanism and
activates other endopeptidases
■ Trypsinogen to trypsin
(breaks down basic AA)
■ Chymotrypsinogen to
chymotrypsin (breaks down
aromatic AA)
 ■ Procarboxypeptidase to ● The absorbed amino acids are usually in the
carboxypeptidase portal vein and directed to the liver for
■ Proelastase to elastase further processing or used to make new
● For the small intestine, there are also proteins
aminopeptidases and dipeptidase
Interorgan Amino Acid Exchange
Peptide Uptake and Absorption ● Amino Acids
● Occurs in the small intestines (from the lumen ○ Smallest products of the GIT protein
to mucosal cell) digestion and the primary source of
● There is another set of peptide bond nitrogen in the body
cleavage, especially for peptides with more ○ Found intracellularly and in the
than three amino acids circulation
● Pumps ○ Normally, amino acids obtained from
○ Na-K ATPase Pump the cellular and tissue protein
■ 3 Na, 2 K breakdown are 2-3 fold more than
○ Na-H Pump dietary protein
○ Na-AA Pump ● A normal adult mammal degrades 1-2%
● Larger peptides are poorly absorbed and percent of their body protein daily, mostly
further hydrolyzed by brush border from the liver or other visceral organs
peptidases ● Protein turnover occurs in other different
● Once larger peptides are hydrolyzed into free tissue types at different rates
amino acids or smaller peptides, they can ○ Half-lives of immunoglobulins and
then be absorbed intact in the mucosal cells collagen: measured in years
○ Certain small biological active ○ Half-lives of liver proteins and
peptides exert effects, even if given regulatory enzymes: measured in
orally hours to days
● Generally, oligopeptides enter the apical ○ Proteins of visceral organs turnover at
aspect of enterocytes via proton-dependent a faster rate than those of the skeletal
transporters (H-AA PepT1) muscles and connective tissues
● Free amino acids and small peptides enter via ■ In the latter phases of
carrier-mediated processes, such as physiological starvation
sodium-dependent transporters (Na-AA) during cachexia, muscle
● Once inside the cytoplasmic compartment of protein is degraded at a
the intestinal mucosal cells, these peptides faster rate due to lack of
can either be further hydrolyzed by energy source
intracellular peptidase or diffuse directly into ● 75% of amino acids generated from tissue
the portal blood proteins digestion are used for the
○ Aminopeptidase and dipeptidase re-synthesis of new tissue proteins, while the
seen in the enterocytoplasm remainder enter hepatic gluconeogenesis
● L-amino acids are absorbed by and/or ketogenesis
carrier-mediated mechanisms that require ● Amino acids removed from the tissue pool are
sodium, while D-amino acids are apparently placed through the digestion of dietary
transported only via passive diffusion protein and from de novo biosynthesis in the
○ L-amino acids are physiologically cells
found in mammals ● Amino acid, unlike glucose and fatty acids,
○ Bacterial cell wall proteins contain are stored in the body in a functional capacity
D-amino acids ○ Amino acids are continually utilized,
○ For glucose or carbohydrates, it is or removed from the body when in
D-glucose (dextrose) excess (e.g., uric acid or creatinine
● Amino acid products pass through the production or loss/secretion through
basolateral membrane aspect of the the urine)
enterocytes through the interstitial fluids and
into the blood vessels for systemic distribution