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Metabolic disorders exam 2 (LA)
vitamins, what dont they do
176
Veterinary Medicine
Graduate
12/01/2011

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Cards

Term
What part of the pituitary gland is affected in patients with equine cushings syndrome?
Definition
pars intermedia

*** equine cushings syndrome aka pituitary pars intermedia dysfunction (PPID)
Term
T/F equine PPID is a neurogdegenerative condition that results from failure of the pars intermedia to secrete proopiomelanocorticoids (POMC)
Definition
FALSE

PPID results from OVERSECRETION of POMC hormones
Term
What is the pathophysiology of PPID?
Definition
idiopathic degeneration of inhibitory neurons in the hypothalamus ---> loss of inhibition in the pituitary --> hypertrophy of the pituitary gland with over-secretion of POMC hormones by pars intermedia
Term
What are the types of endocrine cells located in the pars intermedia of the pituitary? What is the function of their endocrine products?
Definition
melanotropes

*** these cells produce proopiomelanocortin (POMC) which is a precursor for several different protein hormones including ACTH (response to stress), melanocyte stimulating hormone (energy homsotasis), endrophins, and corticotrophin-like intermediate peptide (glucose metabolism)
Term
What season is associated with a peak in clinical signs related to PPID?
Definition
FALL

**** levels of POMC peptides rise in normal and PPID horses in the fall, perhaps in preparation for the high energy demands of winter
Term
What is the typical presentation of a horse with PPID?
Definition
older animal (40% of geriatric horses!)

abnormal fat deposits (above the eyes) with muscle wasting (neck and back, pot belly), hirsutism, persistent sweating, laminitis, PU/PD
Term
What concurrent disease may present in horses with PPID prior to the development of classical clinical signs like hirsutism or sweating?
Definition
laminitis!

*** esp. in horse that have PPID + insulin resistance
Term
What is the pathologic mechanism of PU/PD in horses with PPID?
Definition
insulin resistance --> hyperglycemia --> osmotic diuresis

and/or reduced secretion of ADH from the posterior pituitary (not completely elucidated, perhaps secondary to pressure necrosis or impaired hypothalamic control)
Term
If you see an old horse with chronic non-responsive bacterial infections should you also assess them for what metabolic disease?
Definition
PPID!

increased endorphins from elevated POMC cause immunosuppression and persistent sweating causes skin maceration which increases the risk of dermatitis
Term
What is the pathophysiology of insulin resistance in horses with PPID?
Definition
abnormal glucocorticoid regulation
Term
If you are presented with a horse with hirsutisim and other classical signs of PPID why would you still want to run diagnostic tests?
Definition
to monitor response to therapy and guide any adjustments that need to be made

and to r/o concurrent insulin resistance
Term
What test is most commonly used to diagnose and monitor PPID?
Definition
endogenous ACTH

*** requires a single plasma sample, less risk of inducing laminitis than the dex suppression test, both of these tests have similar lack of sensitivity early in the disease process
Term
What finding on dexamethasone suppression test is associated with PPID?
Definition
post dex levels of cortisol >1 ug/dl

*** in normal animals an injection of dexamethasone should exert negative feedback at the pituitary resulting in a low cortisol level. Remember, PPID horses are over-secreting POMC due to a loss of hypothalamic inhibition.
Term
Why might you want to try a treatment trial in a horse that had normal values of endogenous ACTH or dexamethasone suppression test?
Definition
both tests have low sensitivity in early stages of the disease

*** it is not unusual to treat in the absence of a definitive diagnosis if clinical signs warrant therapy
Term
What is the treatment for PPID?
Definition

Pergolide mesylate (Dopaminergic receptor agonist, mimics the function of degenerate hypothalamic neurons to restore normal inhibition to the pars intermedia)

 

supportive --> clip hair coat, good preventative medical care due to immunosuppression

 

if insulin resistant --> minimize dietary starch and sugar

Term
How long should horses with PPID be treated with pergolide?
Definition
for LIFE!

often need higher doses as they age and neurodegeneration increases, monitor effectiveness of dose with endogenous ACTH q 6-12 months
Term
What formulation of pergolide has the best shelf-life and bioavialablity?
Definition
powder formulation
Term
T/F although goiters are pretty common in horses they are not always associated with abnormal thyroid function
Definition
TRUE

*** r/o thyroid cyst or neoplasia with ultrasound +/- biopsy
Term
Which form of thyroid hormone is most metabolically active?
Definition
T3

*** remember, both T3 and T4 circulate in the blood either bound to protein or "free" (active)
Term
Why are thyroid stimulation tests not widely used in horses even though these tests are the best means of assessing thyroid pathology?
Definition
TRH/TSH is NOT commercially avialable and there is not a lot of data on interpretation of results

*** usually just measure free T3 and T4
Term
Although hyperthyroidism is extremely rare in horses it has been documented in association with what concurrent disease process?
Definition
thyroid neoplasia

*** Dx -> elevated free T3/T4, Tx -> surgical excision of the tumor
Term
What is the most common reason for measuring low T3 in a horse?
Definition
nonthyroidal illness syndrome

*** can be incited by systemic illness, drugs, and some nutritional protocols, ALWAYS test Free T4 as well as T3
Term
T/F there is NO indication for supplementing thyroxine in cases of nonthyroidal illness syndrome
Definition

TRUE!!!!!!!

 

*** tx is potentially associated with risks (osteoporosis, atrial fib, CHF) and conveys NO benefit in animals without primary hypothyroidism

Term
What is the most common cause of true hypothyroidism in horses?
Definition

congenital

 

*** occurs if the dam's diet is insufficient or excessive in iodine, or contains high levels of nitrates --> impairs fetal thyroid function --> musculoskeletal abnormalities (mandibular prognathism, impaired cuboidal bone ossification, flexural deformities, underdeveloped pectorals) and increased risk of FPT. Foals rarely respond to exogenous thyroxine, require extensive nursing care, prognosis is poor

Term
What is the only common indication for use of levothyroxine in horses?
Definition
treatment of obesity related insulin resistance

** levothyroxine improves insulin sensitivity and facilitates weight loss. Used short term until target body condition score is reached
Term
What animals are at higher risk of developing hyperlipemia?
Definition
ponies/mini horses, donkeys and camelids

*** all are predisposed to excessive fat mobilization following periods of sustained anorexia
Term
What is the difference between hyperlipidemia and hyperlipemeia?
Definition
hyperlipidemia --> mild to moderate elevations in serum triglycerides

hyperlipemia --> massive mobilizations of fat (TG> 500 mg/dl) --> can progress to hepatic lipidosis
Term
What serum TG values are diagnostic for hyperlipemia?
Definition
>500mg/dl

serum or plasma often appears opaque white/yellow
Term
What enzyme is responsible for conversion of adipose tissue into FFAs?
Definition

hormone-sensitive lipase

 

*** present in the cytoplasm of adipocytes and is activated by a low insulin/glucagon ration (ie. negative energy balance)

Term
What life threatening complication can occur in patients with hepatic lipidosis?
Definition
the liver may rupture resulting in life-threatening hemorrhage
Term
What are the four principles of therapy for treatment of hyperlipemia? What is the prognosis?
Definition
treat underlying cause of anorexia

restore positive energy balance (increase energy availability with NG -> enteral or TPN AND reduce energy requirements (wean or abort))

Insulin (regular CRI, IM long acting) --> inhibits hormone sensitive lipase (breaks down adipose into FFA) and activates lipoprotein lipase (pulls FFAs out of plasma and into adipocytes)

manage liver insufficiency

Prognosis depends on severity at presentation, early aggressive treatment is best hope for a positive outcome
Term
What are the three components of equine metabolic syndrome?
Definition
obesity or regional adiposity

insulin resistance

subclinical or clinical laminitis
Term
Where should you evaluate fat cover/body condition on a horse?
Definition
neck
tail head
withers
back/rump
ribs
shoulder
Term
which tissues develop insulin resistance (IR)?
Definition
skeletal muscle
liver
adipose tissue

*** IR occurs secondary to down regulation of insulin receptors +/- reduced intracellular signaling in response to the binding of insulin by any remaining receptors
Term
What is the difference between compensated and uncompensated insulin resistance? Which form is most commonly encountered in horses?
Definition
most common form in horses is compensated: increased insulin, normal blood glucose <-- more insulin needs to be secreted to maintain BG due to decreased effectiveness (less receptors and less response to ligand binding).

uncompensated: hyperglycemia +/- increased insulin (this reflects some degree of pancreatic endocrine insufficiency with inadequate secretion of insulin to maintain glucose homeostasis)
Term
T/F not all obese horses are insulin resistant, not all insulin resistant horses are obsese
Definition

TRUE

 

pathophysiology of IR is complex! However; obesity is a significant RISK factor for development of IR because it increases systemic inflammatory responses that reduces insulin sensitivity

Term
What is the proposed mechanism for development of laminitis in association with insulin resistance?
Definition

laminar cells have high glucose requirements -> IR results in impaired ability for the cells to take up adequate glucose for their metabolic needs

 

hyperinsulinemia affects laminar blood flow which can also result in laminitis

Term
What is the major differential diagnosis for equine metabolic syndrome?
Definition
PPID <-- r/o with endogenous ACTH

** it is possible for horses to have both of these conditions concurrently
Term
What are some indicators of subclinical laminitis?
Definition
abnormal horizontal growth rings on the hoof or misshapen hooves

radiographic findings of P3 rotation/sinking and remodeling of distal aspect of P3
Term
How do you diagnose insulin resistance in horses?
Definition
fast for 6 hours and take a blood sample to measure serum insulin and glucose -->

insulin > 20 micrograms/ml suggestive of IR (>30 = hyperinsulinemia)

glucose is normally high normal (remember, most common form of IR in horses is compensated <-- the animal produces a lot of insulin to maintain glucose homeostasis due to decreased tissue sensitivity)

*** delay testing if the horse has acute laminitis as stress and pain will artificially elevate both insulin and glucose values
Term
What test is more sensitive for diagnosing IR than measuring a single fasted insulin and glucose?
Definition
combined glucose-insulin test: administer specific dose of glucose and insulin and track BG over the course of 2.5 hours --> if high BG persists longer than 45 min the horse has insulin resistance
Term
What drug can lower serum levels of T3 and T4?
Definition
phenylbutazone <-- so lots of horses with laminitis may have low thyroid values which ARE NOT associated with primary hypothyroidism but rather with NSAID therapy
Term
How can you manage insulin resistance in horses?
Definition
promote weight loss!

diet (NO starch/sugar <- pasture grass, grain, apples, carrots etc. and high fiber <- cold water soaked grass hay @ 1.5-2% of target body weight)

short course of levothyroxine to increase basal metabolic rate until target body weight has been attained

manage laminitis
Term
What are some risk factors for the development of heat stress in camelids?
Definition
high environmental heat and humidity (esp. in temp + % humidity greater than 150)
increased activity, transportation or stress
heavy fiber cover and obesity
late gestation or lactation
Term
What are the fiber-less areas of a camelid?
Definition
ventral abdomen
axillary space
inguinal and perineal regions

*** these areas also contain sweat glands to facilitate evaporative cooling
Term
What is the common clinical presentation of a camelid with heat stress?
Definition
recumbent, ptyalism, rectal temp > 105
Term
What are the most important differential diagnoses for heat stress in camelids?
Definition
P. tenuis CNS migration (eosinophilia on CSF tap)

meningitis/encephalitis (leukocytosis)

traumatic injury
Term
What is the most important element of therapy for heat stress in camelids to influence towards a positive outcome? What adjunctive therapies are available?
Definition
EARLY TREATMENT

shear fiber and normalize core body temp, fluids for dehydration and acidosis, plasma if hypoprotinemic, NSAIDs, broad spectrum antibiotics (predisposed to secondary pneumonia), vit E and selenium PO
Term
What is a major complication of heat stress in camelids?
Definition

multiple organ system failure, esp. pulmonary edema

 

*** pulmonary edema occurs in association with hypoprotinemia, always check TP in heat stress patients and treat with IV plasma as needed. Temporary infertility (scrotal edema and decreased sperm quality in males and abortion and premature birth in females are also associated with heat stress

Term
What is the best way to reduce risk of heat stress in camelids?
Definition
Shearing before June 1st every year!

Also, provide ample shade, water and free choice electrolytes, fans at floor level, moistened sand bedding, pools, pasture grazing requires less energy than hay to digest, MONITOR for depression and scrotal edema, and breed so that they give birth in the spring
Term
Where do you assess body condition on a camelid?
Definition

withers, between the rear legs, chest (remember, obese animals are at increased risk for heat stress)

 

*** don't assess body condition at the pelvis as ALL camelids have little fat and muscle in this area

Term
What chemistry value should you always assess in a sick camelid?
Definition
triglycerides, camelids are very susceptible to stress hyperlipemia (>60 mg/dl)
Term
What are the fat soluble vitamins and what are their primary sources?
Definition
A, D, E, K

all are found in high levels in fresh forage (and diminishing as forage is dryed and stored). Additionally vit K is synthesized in adequate quantities by the rumen microflora
Term
What is the normal function of vitamin A? What conditions are associated with a deficiency?
Definition
opthalmic (supports low light vision -> deficiency results in keratitis/uveitis/blindness)

Reproductive (supports spermatogenesis and fetal development --> deficiency results in stillborn/weak calves and retained placenta)

maintenance of epithelial tissue and skeletal muscle (deficiency --> diarrhea, anorexia, wasting/weightloss)

Cell mediated immunity (supports neutrophil function. Deficiency -> immunosuppresion)
Term
What is the normal function of vitamin D? What conditions are associated with a deficiency?
Definition
Ca:P ratio (vit D enhances GI absorption of Ca and P, and facilitates normal mineralization of organic bone matrix)

deficiency -> low serum Ca and P --> rickets (young) and osteomalacia (old) ---> lameness and pathologic fractures
AND decreased milk production + fertility
Term
How is vitamin D metabolized to its active form?
Definition
precursors are ingested in plant material or synthesized in the skin -> converted to 25(OH)vit D in the liver -> converted to active form 1,25(OH)2 vit D in the kidney
Term
How does vit D toxicity manifest?
Definition
dystrophic mineralization of kidneys, aorta, abomasum, and bronchioles --> renal manifestation as PU is common
Term
What is the most biologically active form of Vitamin E? Why is toxicity rare?
Definition
alpha- tocopherol is most active form, due to very limited absorption from the gut Vit E toxicity is rare
Term
What is the normal function of vitamin E? What conditions are associated with a deficiency?
Definition
antioxidant (deficiency -> white muscle disease)

increased cell mediated immunity, neutrophils and macrophages (deficiency -> immunosuppression)

supports increased fertility (deficiency --> retained placenta)
Term
What is the normal function of vitamin K? What conditions are associated with a deficiency?
Definition

supports protein synthesis esp. clotting factors 2 (prothrombin), 7, 9, 10

 

Deficiency is rare because vit K is synthesized by rumen microbes. Occasional cases associated with ingestion of moldy sweet clover and dicoumarol toxicity --> tissue hematomas and can progress to overt hemorrhage and death

 

*** r/o hemorrhagic BVD w/CBC. If dicoumerol toxicity there will be no thrombocytopenia

Term
Although vitamin B is readily synthesized by rumen microbes in large quantities which two B vitamins are routinely supplemented and why?
Definition
Niacin (B3) --> mitochondrial respiration (ATP), nutrient metabolism, anti-lipolytic (decrease FFA release from adipose tissue -> reduce risk of ketosis and hepatic lipidosis)

Biotin (B7) -> enzyme cofactor, promotes hoof/horn health
Term
What is the pathophysiology of polioencephalomalacia? What is the therapy?
Definition
Thiamine (B1) deficiency that can occur in ANY ruminant species

either ingestion of pre-formed plant thiaminase or excessive grain intake favors overgrowth of thiaminase producing rumen bacteria --> deficiency results in cerebral cortical necrosis and a wide variety of neurologic signs

tx: parentral thiamine +/- dexamethasone (reduce cerebral edema)
Term
What are the three major functions of macrominerals?
Definition
structural components of bone, tissues, and body fluids

vital in acid-base status
maintenance, osmotic potential

membrane electric potential and nerve
transmission
Term
What are the two major functions of microminerals?
Definition
components in enzymes or
enzyme cofactors

components in hormones
Term
What is the normal function of calcium? What conditions are associated with a deficiency?
Definition

mineral component of bone (deficiency --> rickets and osteomalacia)

 

enhances neurotransmission and

skeletal/cardiac muscle contractility (acute peripartum deficiency --> milk fever)

 

blood clotting

 

milk production

Term
What hormones are responsible for maintaining calcium phosphorus homeostasis?
Definition

Parathyroid hormone (PTH): elevates serum calcium by increasing osteoclastic activity --> calcium is released from bone, increasing calcium resorption in the kidney, and stimulating renal conversion of vit D to active form (1,25(OH)2 vit D) which increases active gut absorption of calcium. Lowers serum phosphorus by enhancing renal and salivary excretion.

 

Calcitonin: lowers serum calcium by reducing osteoclastic activity and promoting renal excretion of calcium.

Term
Calcium toxicity can decrease absorption of which micromineral? What about potassium toxicity?
Definition
calcium toxicity --> zinc deficiency

potassium toxicity --> magnesium deficiency

**** mechanism for both is decreased gut absorption
Term
What is the normal function of phosphorus? What conditions are associated with a deficiency?
Definition

mineral component of bone matrix (deficiency --> rickets in young and osteomalacia in adults)

 

component of integral cell molecules (ATP, DNA, phospholipid) --> deficiency results in intravascular hemolysis and hemoglobinuria milk production

Term
Rickets can arise from deficiencies in which three important nutritional components? What is the pathophysiology of this disease?
Definition
calcium, phosphorus, and/or vitamin

failure of normal bone mineralization --> pathologic fractures AND abnormal articular cartilage formation --> swollen painful joints and lameness
Term
What is the normal function of potassium? What conditions are associated with a deficiency?
Definition
maintenance of osmotic pressure and acid-base homeostasis (major intracellular electrolyte)

nerve transmission and muscular contraction (deficiency --> marked muscle weakness and recumbency)

enyzmes and cofactors for protein synthesis and CHO metabolism (deficiency --> weightloss and lethargy)
Term
What is the normal function of sodium? What conditions are associated with a deficiency?
Definition
major extracellular cation --> maintains extracellular fluid volume and acid-base status

facilitates neuromuscular transmission

extreme deficiency -> neuro and cardiac dysfunction
Term
Toxicity of what two macrominerals can cause prepartum udder edema?
Definition
sodium and potassium (important for osmotic pressure homeostasis)
Term
What is the normal function of copper? What is the most accurate way of assessing body stores of copper?
Definition

enzyme component (electron transport for aerobic respiration, melanin production, cross-links collagen, iron absorption -> hemoglobin synthesis, facilitates phagocytosis)

 

copper is stored in the liver, assess body levels of copper via liver biopsy (NOT serum sample)

Term
What clinical signs are associate with copper deficiency?
Definition

loss of hair pigmentation (necessary for melanin production)

lameness, heel cracks (cross links collagen)

 

hypochromic microcytic anemia (necessary for iron absorption and hemoglobin production)

 

immunosuppression (necessary for phagocytosis)

 

scours, poor growth, impaired fertility and cardiac function (necessary for aerobic respiration)

Term
What mineral is most likely to be oversupplemented? What are some signs associate with toxicity?
Definition

copper!

 

acute toxicity: neurologic, dyspnea, gastroenteritis

 

chronic oversupplementation: large volumes of copper accumulate in the liver -> stress results in massive release of copper into the blood -> hemolytic crisis (icterus, hemoglobinuria, widespread necrosis)

Term
What is the function of iodine?
Definition
synthesis of thyroxine and triiodothyronin --> regulate energy metabolism
Term
What feed materials are goitrogens (interfere with iodine absorption and/or thyroid hormone synthesis/secretion)?
Definition
cyanogenic -> raw soybeans, beet pulp, corn, sweet potato, white clover (supplement diet with iodine when feeding these materials)

progoitrins --> kale, rape, cabbage, turnip, mustard (minimize/remove from diet)
Term
What is the impact of a marginal iodine deficiency in a pregnant cow?
Definition
hairless, stillborn or weak calves +/- goiters (gland hyperplasia occurs in response to excessive TSH)
Term
What is the normal function of manganese? What conditions are associated with a deficiency?
Definition
component of mucopolysaccharides and glycoproteins in bone and cartillage (deficiency --> skeletal abnormalities and reduced growth rate in neonates)

antioxidant (superoxide dismutase)
Term
over supplementation of which micromineral mimicks copper deficiency (bleached hair coat, scours etc.)?
Definition
molybdenum --> reduces copper absorption
Term
What is the function of selenium and what is the major source?
Definition
antioxidant (glutathione peroxidase), improves neutrophil function, component of enzyme involved in conversion of T3 to T4

major source is from soil -> plants. East of mississippi or west of rockies is associated with low soil selenium content <- FDA limits supplementation to 0.3 mg/kg of DM
Term
White muscle disease is the result of what nutritional deficiency? Describe the clinical presentation and diagnostic findings associated with this disease.
Definition
selenium and/or vit E deficiency --> acute muscle weakness, dyspnea and cardiac failure

Dx by measuring serum glutathion peroxidase activity (serum selenium levels are less accurate)
Term
What organ system is affected by selenium deficiency in adults?
Definition
reproductive --> abortions/stillbirths, retained fetal membranes, abnormal estrus cycles, metritis and mastitis

also generalized immunosuppression
Term
Blind staggers results from toxicity of what micromineral? What clinical signs are associated with this disease?
Definition
selenium toxicity --> sloughed hooves + lameness, hair loss, emaciation and death
Term
What dietary components can impair zinc absorption? What clinical signs are associated with deficiency?
Definition

copper, iron, cadmium and calcium can all reduce zinc absorption

 

deficiency -> impaired reproductive capacity (diminished spermatogenesis, altered prostoglanin synthesis), immunosuppression, parakeratosis of legs, nostrils, and neck, weak hoofs --> lameness

Term
What are five ways of supplementing the diet with vitamins and minerals?
Definition
add supplements to diet (TMR, free choice, or top dressing)

parentral injections (ex. Vit A,D,E, and selenium for neonates or pre-calving to the cow)

intra-ruminal bolus (selenium)

fertilization of the pasture

selection of specific feeds that contain large quantities of desired mineral/vitamin
Term
What are the three products of microbial digestion in the rumen?
Definition
volatile fatty acids (from microbial fermentation of protein and CHO)

B vitamins

microbial protein (any rumen microbes that are washed out of the rumen and into the abomasum undergo enzymatic digestion --> cow uses these amino acids for milk and tissue protein synthesis)
Term
Which type of rumen microbes prefer an acidic environment?
Definition
microbes that digest sugar and starch prefer acidic environment *** ALL other rumen microbes like it neutral (pH 6.0-7)
Term
What are the three types of volatile fatty acids produced in the rumen and what are their major metabolic functions in the cow?
Definition
in order of highest production to least:

Acetate (fiber digestion -> milk fat)

Propionate (sugar and starch digestion -> glucose production in liver and lactose production in the mammary gland)

Butyrate (fiber + starch digestion -> milk fat and glucose)
Term
How much of the cow's energy is provided by volatile fatty acids?
Definition

60-80% (proprionate + butyrate)

 

*** remember, acetate really only contributes to milk fat synthesis

Term
If the cow gets most of its energy from VFAs and most of its protein from microbial protein why do we feed cows CHO and protein?
Definition
need to optimize rumen microbe growth by providing adequate growth substrates (including CHO and protein)
Term
Why should you start increasing nutrient content of the diet in a cow 3-4 weeks prior to partuition?
Definition
need to adapt rumen microbes (to microbes that metabolize lactate, 3-4 weeks) and papillae ( to better absorb increased levels of VFAs, 4-5 weeks) to lactation diet. Need to ensure high nutrient density as feed intake is depressed prior to calving but energy requirements are elevated (ex. milk production)

*** abrupt transition to high starch diet at time of calving will result in accumulation of lactate and VFAs -> rumen aciosis
Term
What seven diseases are commonly associated with partuition in cows?
Definition
milk fever (hypocalcemia)
dystocia
retained placenta
metritis
ketosis
hepatic lipidosis
displaced abomasum
Term
Which three ketone bodies are abnormally elevated in patients with ketosis?
Definition

acetoacetic acid

acetone

Beta-hydroxybutyrate (BHB)

Term
What is the pathophysiology of ketosis and hepatic lipidosis?
Definition
decreased blood glucose (lower feed intake + metabolic demands of late trimester fetus and lactation) --> decreased insulin:glucagon ratio --> activated hormone-sensitive lipase which mobilizes FFAs (aka non-esterified fatty acids, or NEFAS) from adipose tissue and into circulation --> NEFAS are transported to the liver and converted into triglycerides which overwhelm hepatic capacity to either export as lipoproteins (hepatic lipidosis) or convert into ATP via the TCA cycle (ketosis)
Term
How are FFAs converted into ketone bodies in the liver?
Definition
FFAs are converted into ketone bodies by Acetyl-CoA
Term
What percent of the normal liver parenchyma is fat? What about patients with hepatic lipidosis?
Definition
normal --> <5% fat

hepatic lipidosis --> >34% fat (visible histologically as large vacant vacuoles within hepatocytes)
Term
What tissues can use ketone bodies as an alternative energy source (ie. other than glucose) for the TCA cycle?
Definition

Heart, skeletal muscle, and kidney

 

**** NOT liver or brain!!!

Term
How are ketones excreted from the body?
Definition
excreted in milk or urine
Term
Why do both ketosis and hepatic lipidosis act to exacerabte the condition once initially incited?
Definition
high levels of ketones suppress appetite which further contribute to the negative energy balance resulting in even more FFA mobilization from adipose

AND

as triglycerides accumulate within hepatocytes normal liver function is impaired which further reduces the liver's capacity to deal with the influx of FFAs
Term
Why is hepatic lipidosis also called Fat Cow Syndrome?
Definition
over conditioned animals are much more likely to have lower feed intake after calving AND already have extensive adipose tissue to support massive FFA mobilization in response to negative energy balance

*** older cows are also at increased risk because they tend to be the highest producing cows and therefore have the greatest energy requirements
Term
Although ketosis normally presents with non-specific GI signs (anorexia, reduced rumen motility, scant dry feces) 10% of cases can present with neurologic deficits. What are the two potential causes for the CNS signs?
Definition
hypoglycemia

and/or

isopropyl alcohol (from breakdown of the ketone acetoacetic acid in rumen)
Term
If you diagnose ketosis on the basis of ketonuria or ketolactia what should be your next step?
Definition
look for a primary concurrent disease (ie. something other than recent partuition that could incite the negative energy balance)

**** remember, primary ketosis is definitely possible, just want to make sure there is no concurrent disease because failure to identify and resolve this will result in inability to effectively manage the ketosis
Term
What is the gold standard for diagnosing ketosis?
Definition
Blood BHBA (blood β-hydroxybutyrate)

*** but this test has a longer turnaround and is much more expensive than measuring ketones in the urine or milk
Term
Other than measuring ketone, FFA, and triglyceride levels in the serum, what other two laboratory tests are avialable for the diagnosis of ketosis and hepatic lipidosis?
Definition
liver biopsy

sulfobromophthalein dye extraction (positive if T1/2 > 4 min, guarded prognosis if > 9 min)
Term
What is the prognosis for ketosis and hepatic lipidosis?
Definition
for primary ketosis that is diagnosed early and managed approprtiately prognosis is great

for hepatic lipidosis or protracted cases of ketosis prognosis is poor to grave
Term
What is the difference between type 1 and type 2 ketosis?
Definition
Type 1 occurs later into lactation (3-6 weeks) and is the result of inadequate caloric density of the diet, not commonly associated with hepatic lipidosis (so better prognosis)

vs.

Type 2 occurs early in lactation (1-2 weeks) and is associated with insulin resistance and increased adipose sensitivity to hormone sensitive lipase --> greater FFA mobilization and incidience of hepatic lipidosis --> worse prognosis
Term
What is the cornerstone of treatment for ketosis and hepatic lipidosis?
Definition

GET HER EATING!!!!

treat any primary diseases, offer highly palatable feed +/- transfaunate or force feed if refractory to medical management (IV glucose, glucocorticoids, and B vitamins) after 2-3 days of therapy

 

*** may also try giving long-acting insulin with the IV dextrose to enhance tissue uptake of glucose and minimize FFA mobilization in refractory cases

Term
Why are glucocorticoids used to treat ketosis and hepatic lipidosis?
Definition

stimulate gluconeogenesis by enhancing mobilization of precursors (ie. amino acids)

 

reduce milk production

 

stimulates appetite

Term
What is a good way to monitor for subclinical ketosis in fresh cows (ie. 0-4 weeks post partum)?
Definition
obtain 12 represenative serum samples prior to feeding --> measure BHB (serum beta-hydroxybutyrate) --> if over 20% of the cows tested have a BHB > 1400 ketosis is a problem
Term
How can you prevent ketosis and hepatic lipidosis in cattle?
Definition
prevent obesity (esp. in late lactation/dry period)

feed highly digestible and palatable diet in late gestation/early lactation (important to begin 3-4 weeks prepartum to allow rumen microbes and papillae to adapt to higher starch substrate and VFA production)

+/- supplement diet with niacin (substrate for TCA cycle)
+/- propylene glycol drench for individual high risk animals <-- do use this to treat pregnancy toxemia in sheep!
Term
What are some supplements that can be added to the diet to minimize subclinical ketosis?
Definition
Niacin (ATP susbstrate)

choline (necessary for lipoprotein production in the liver)

monensin (off-label use --> inhibits growth of gram positive rumen bacteria --> increased propionate production and decreases rumen acidosis) <-- also used to prevent protein-energy malnutrition in beef cows
Term
What is the etiology of protein-energy malnutrition AKA pregnancy toxemia of beef cows? What is the typical presentation of an affected animal?
Definition
negative energy balance in the last 6 weeks of gestation due to increased energy drain by the fetus

affected individuals present with weakness and recumbency (recumbency is a negative prognostic indicator), thin dull coat +/- hypothermia
Term
T/F fatty liver occurs transiently in the early stages of protein-energy malnutrition
Definition
TRUE

*** in advanced disease muscle atrophy and serous atrophy of fat occurs
Term
How much of the maternal glucose is normally consumed by the fetus in an ewe?
Definition
2/3rds!

However, glucose production is usually sufficient to meet fetal and maternal demands given adequate dietary energy
Term
What treatment offers the best hope for recovery in cases of pregnancy toxemia in sheep (aka. ovine ketosis)?
Definition
removal of the fetus(es) either by caesarean section or induced partuition (dexamethasone to stimulate fetal lung maturation and PGF 2alpha 12 hours later)
Term
Other than maintaining healthy BCS and feeding highly digestible and palatable feed in late gestation what other management practice can be used to prevent ovine ketosis?
Definition
ultrasound to diagnose multiple fetuses and group/feed mothers accordingly
Term
Why are periparturient cows at increased risk of developing hypocalcemia?
Definition
increased calcium demands (colostrum and milk + fetal skeleton esp. with multiples <--- this large calcium demand requires a large increase in secretion of PTH to maintain homeostasis
Term
How do early-mid dry period cows meet their calcium demands?
Definition
passive absorption across the gut (ie. NOT vit D mediated)
Term
What are the four major minerals in cow milk?
Definition
Potassium
Calcium
Chlorine
Phosphorus

*** listed in order of largest quantity to least
Term
PTH acts to raise serum calcium through three main mechanisms. What are they and how quickly to they cause serum calcium to rise?
Definition
increase renal resorption (minutes)

stimulate renal activation of vit D (to 1,25(OH)2 Vit D) --> active absorption of calcium across the gut (24 hours)

increases osteoclastic activity (48 hours)
Term
What 5 factors reduce an animals ability to maintain calcium homeostasis?
Definition
REDUCED FEED INTAKE -> decreased passive and active (vit D) absorption across the gut

METABOLIC ALKALOSIS (diets high in K+ and Na+) alter tissue PTH receptor conformation --> impaired renal activation of Vit D and impaired osteoclastic response to PTH

In addition to contributing to metabolic alkalosis, DIETS HIGH IN POTASSIUM reduce magnesium absorption -> reduced PTH secretion and diminished tissue sensitivity to PTH

EXCESSIVE DIETARY PHOSPHORUS -> inhibits renal activation of Vit D

HIGH ESTROGEN-> decreased feed intake (decreased gut absorption) and reduces osteoclastic sensitivity to PTH (decreased bone resorption)
Term
What is the most common signalment for a cow with hypocalcemia?
Definition

multiparous high producing late-gestation/early lactation cow (heifers produce less milk/colostrum and have more labile bone because they're still growing themselves)

 

*** jerseys and guernseys are at increased risk (higher calcium content of colostrum, higher milk production per body weight, fewer intestinal vitamin D receptors)

Term
What are the three clinical stages of milk fever (hypocalcemia) in diary cattle?
Definition
stage 1, prodromal: standing, mild excitement and muscle tremors, tachycardia

stage 2, sternal recumbency: depression, flaccid paralysis, tachycardia (weak/quiet on ascultation), hypothermia, bloat (decreased GI motility), uterine inertia (dystocia or retained placenta)

stage 3, lateral recumbency: same as above + reduced anal/corneal/pupilary light reflexes ---> progresses to coma and death within a few hours if no intervention
Term
How can hypocalcemia predispose a cow to developing other metabolic diseases (ex. ketosis)?
Definition
Calcium is needed for normal muscular contractility, hypocalcemia results in GI stasis --> bloat and decreased feed intake --> increased risk of developing negative energy balance
Term
What is the most common way hypocalcemia is diagnosed?
Definition

suggestive history and signalment (late gestation/early lactation multiparous high producer, esp. jersey/guernsey) + response to treatment

 

*** it is imperative to treat these animals quickly! You should collect blood samples for retrospective serum chem if inadequate response to therapy

Term
In addition to hypocalcemia, what other serum chem values will be abnormal in an animal with milk fever?
Definition
hypophosphatemia (<3 mg/dl): lactation drain, inadequate mobilization from bone (due to insensitivity to PTH), and increased renal and salivary losses (in response to elevated PTH)

hypermagnesemia (>2.2 mg/dl): PTH increases renal reabsorption of magnesium

hyperglycemia: secondary to stress and low insulin (insulin secretion is impaired by hypocalcemia)

high CK (recumbency and partuition)
Term
What is the treatment for hypocalcemia (milk fever)?
Definition
place cow in sternal recumbancy, slow IV calcium borogluconate (avoid using the milk vein) <-- monitor for bradycardia,tachycardia (rebound) and other arrhythmias

affected animals should respond quickly to therapy with the heart beat slowing to a normal rate, and increasing in strength. They will become BAR and regain muscle function. Relapse is common over the next 48 hrs <-- to reduce risk give SQ calcium as well, avoid dextrose (local tissue irritation and abscess formation at injection site), can also supplement with oral solutions/gels
Term
Cow with hypocalcemia are often also hypophosphatemic (lactation drain, inadequate mobilization from bone, and increased renal and salivary losses in response to elevated PTH). Although correction of underlying hypocalcemia often normalizes serum phosphorus patients occasionally need additional supplementation. What form of phosphorus is biologically available?
Definition

sodium monophosphate IV

 

*** do not use hypoposphite salts!

Term
Which type of oral calcium supplementation is safest for use in preventing relapses of milk fever?
Definition
calcium propionate gel

**** less risk of aspiration compared to liquid drenches, less irritation to GI mucosa compared to calcium chloride, propionate is a glucose precursor -> also helps prevent ketosis
Term
What supportive therapies have been used in the past to treat milk fever but are NOT RECOMMENDED currently?
Definition
udder insufflation or skiping milkings --> elevated intramammary pressure reduces milk production (reduces lactational drain on calcium) but HIGH risk of mastitis
Term
Although prophylactic SQ/IV/PO administration of calcium to high risk cows prior, during, and after calving is an effective way of preventing milk fever it is too labor intensive for an entire large herd. What are some strategies for herd prophlaxis?
Definition
monitor incidence of milk fever, if >5-10% of cattle become clinical need to adjust the diet to a negative DCAD (dietary cation-anion difference) diet for the last 3 weeks of gestation --> this causes a compensated metabolic acidosis which allows PTH to bind well to tissue receptors and maintain calcium homesotasis
Term
What traditional mechanism of "prevention" of milk fever in individual animals is NOT RECOMMENDED currently?
Definition
Vit D injections --> either too high a dose resulting in toxicity and irreversible metastatic mineralization of soft tissues

or

lower doses suppress PTH secretion --> further exacerbate hypocalcemia
Term
What anions are important for creating a negative DCAD diet (ie. causes compensated metabolic acidosis which promotes tissue responsivity to PTH)?
Definition

chloride and sulfur

 

these anions incite metabolic acidosis due to the law of electroneutrality (ie. the number of positive and negative charges in a solution must be equal), that is, if we add more anions (Cl- and S-) we need to balance those out with more cations (H+) --> resulting in a more acidic solution

Term
Which cations create a positive DCAD (causes compensated metabolic alkalosis) --> impaires tissue sensitivity to PTH by altering receptor conformation)?
Definition
potassium and sodium

*** we DON'T want this, increases risk of developing hypocalcemia/milkd fever
Term
Which two body systems are responsible for buffering the blood? Which one is more rapid?
Definition

respiratory system -> RAPIDLY compensates for acidosis by increasing respiratory rate to blow off more carbon dioxide (vice versa for alkalosis)

 

kidneys --> SLOWLY excrete cations (if acidosis) or anions (if alkalosis) as needed to regulate plasma pH

Term
How can you monitor the effectiveness of your negative DCAD diet at causing compensated metabolic acidosis?
Definition

monitor urine pH!

 

The kidneys will excrete the additional H+ cations resulting in a lower urine pH (goal is pH= 6.2-6.8 in holsteins, lower in jerseys)

 

*** if urine pH is < 5.5, this indicates uncompensated metabolic acidosis --> decreased feed intake --> risk of ketosis and hepatic lipidosis

Term
What types of forages have low potassium (good for negative DCAD (ie. acidifying) diet)?
Definition
warm season grasses (corn silage) and high fiber concentrate feeds like brewers grains and beet pulp


*** AVOID alfalfa (high K+)
Term
Once you have chosen feed low in potassium and sodium, how can you further reduce DADC to desired level of compensated metabolic acidosis for optimum prevention of milk fever?
Definition

supplement with anionic salts. Chloride salts are more potent acidifiers but are less palatable so tend to choose: Mg-sulfate, Ca-sulfate and ammonium-sulfate

 

*** do a mix of chlorides and sulfates to avoid toxicities (esp. ammonia and Mg) and make sure to provide Calcium at 1% of ration DM

Term
Why is it important to not feed newly fresh cows lactating cow diets?
Definition
these diets contain Na-HCO3 as a rumen buffer ---> causes metabolic alkalosis which alters PTH receptor conformation reducing tissue sensitivity, and can induce milk fever
Term
Hypocalcemia is less common in beef cattle and ewes than it is in dairy cattle due to a lower lactational drain. What are the inciting factors for development of hypocalcemia in these two species?
Definition

occurs late in gestation due to calcium demands of fetal skeletal mineralization (esp. for multiple lambs) often concurrent inadequate feed intake (ie. ketosis) --> reduced intestinal absorption of calcium

 

*** stress can incite hypocalcemia even in lambs and non-pregnant ewes (aka transport tetany)

Term
When do herd outbreaks of hypomagnesemic tetany tend to occur?
Definition
early lactation animals grazing lush pastures (SPRING and FALL)
Term
T/F ruminant body stores of magnesium are primarily in hard tissues (bone/teeth) and are not very labile. All of their magnesium requirement must be provided by their diet
Definition
TRUE
Term
What three factors contribute to the development of hypomagnesemic tetany in ruminants?
Definition
high Mg output (early lactation, older animals - tend to be higher producers, multiple lambs)

low dietary Mg (cool season grasses (ex. wheat, barley, green oats) and high moisture pasture)

inadequate GI absorption of dietary Mg (high dietary K+ impairs Mg absorption; high moisture forage increases rate of passage through GI resulting in diminished absorption; high rumen pH (>6.5) associated with a high forage diet reduces Mg solubility)
Term
How does age affect a ruminant's ability to absorb Mg across the GI tract?
Definition
< 2 months, can absorb Mg across rumen, SI and LI

over 2 months can only absorb Mg from rumen and LI

*** this is why calves can become deficient in Mg if they are only fed milk over the age of 2 months (ex. veal calf)
Term
What is the pathophysiology of hypomagnesemic tetany?
Definition

Mg drain from lactation exceeds dietary intake/absorption --> Mg is depleted from CSF and extracellular fluid --> lowers CNS and PNS membrane potentials closer to threshold AND induces excessive acetylcholine release at neuromuscular junction AND impairs muscle relaxation---> hyperexcitability, convulsions, and tetany

 

*** Mg deficiency also reduces PTH secretion and can incite hypocalcemia (flaccid paralysis)

Term
Why are plasma magnesium measurements not always an accurate assessment of serum levels?
Definition

hypomagnesemia incites episodes of tetany which can cause muscle damage resulting in leakage of intracellular Mg and falsely normalized serum Mg levels

 

*** CSF Mg is a more stable indicator hypomagnesemia

Term
What other serum chem abnormalities are commonly associated with hypomagnesemia in ruminants?
Definition

hypocalcemia

hypophosphatemia

hyperkalemia

elevated AST and CK (secondary to muscle damage as a result of recumbency, tetany, and seizures)

Term
What is the treatment for hypomagnesemic tetany?
Definition
slow IV calcium with 5% magnesium-hypophosphate

response to therapy is much slower (3-5 hours) than with hypocalcemia. Can do Mg sulfate enema and oral supplementation (once swallow reflex is present) to prevent relapse
Term
What are some methods for prevention of hypomagnesemic tetany?
Definition
remove from pasture and/or supplement Mg

supplement pasture with dry hay (increase ingesta transit time --> increase Mg absorption)

select pasture grasses with high Mg content (fescue, legumes) and don't put animals on pasture until it is more mature (10 inches, higher Mg content)

avoid using potassium rich fertilizers (K+ interferes with active Mg absorption across the rumen)

*** if you have a clinical case of hypomagnesemic tetany immediately supplement the entire herd!
Term
How long does a cow need to be recumbent to be labeled a "downer"? And when in the lactation cycle do most cases occur?
Definition
> 24 hours after initial recumbency and after treatment for primary medical problems

most cases occur within the first 100 days of lactation
Term
What are the three main categories of disease that cause primary recumbency?
Definition
METABOLIC DISEASE (hypo- Ca/P/K/Mg; hepatic lipidosis; starvation)

TRAUMA (dystocia; fractured pelvis/long bones; coxofemoral dislocation; nerve damage)

SEPTIC SHOCK (mastitis; metritis; displaced abomasum)
Term
prolonged periods of recumbency due to underlying disease (metabolic, trauma, shock) progress to secondary recumbency through which pathophysiologic mechanisms?
Definition
ischemic necrosis of muscles on the "down" limbs (esp. gastrocnemius and semitendinosus)

pressure necrosis of nerves (esp. peronial branch of sciatic --> knuckling over at the fetlock)

**** secondary recumbency can result in musculoskeletal damage (fracture, ruptured muscle/lig) as the cow struggles to rise, resulting in long-term tertiary recumbency
Term
How do serum CK values correlate with prognosis for downer cows?
Definition

They dont!

 

**** after 48 hours of recumbency CK values will decline rapidly even in downer cows. Best prognostic indicator is clinical observation (although if CK is greater than 10x reference range things are not looking good)

Term
Although CK values have limited prognostic value in downer cows, what combination of CK values and clinical observations are associated with a grave prognosis?
Definition
CK > 10x reference ranges with recumbency > 2-3 days duration
Term
What urinalysis abnormalities are associated with downer cow syndrome?
Definition
protinuria (really myoglobinuria due to skeletal muscle ischemic necrosis)

+/- ketonuria (esp. if associated with primary metabolic disease)
Term
Other than trying to resolve underlying disease (metabolic, traumatic, septic shock), what adjunctive therapies are available for treatment of downer cows?
Definition

NSAIDS and steroids (reduce inflammation, analgesic)

 

deep bedding, roll q 4-6 hours, lifting devices (only if animal can support own weight once standing) or aquatank, place feed and water in easy reach

 

**** be aware of milk and meat withdrawal times, dexamethasone is the only one with no withdrawal for meat or milk

Term
What is the prognosis for a downer cow?
Definition
frequently guarded but depends on cause and duration of recumbency

*** many die within 7-10 days due to sepsis or shock (mortality 20-67%)
Term
What are some strategies for preventing downer cow syndrome?
Definition
PREVENT METABOLIC DISEASE (excellent nutritional management, monitor closely for development of any metabolic derangements and provide prompt therapy)

PREVENT TRAUMA (good footing with adequate bedding, good dystocia management, good system for calmly and safely moving cattle)
Term
How is bovine somatotropin manufactured for commercial use?
Definition
recombinant DNA technology

*** this is the same process used to manufacture other protein hormones for medical use (insulin, interferon etc.) as well as rennin for cheese manufacturing
Term
T/F recombinant bovine somatotropin (rbST) is available over the counter in all 50 US states
Definition
TRUE

** estimated that around 33% of cows in US herds are managed with rbST
Term
What is the difference between homeostasis and homeorhesis?
Definition
homeostasis refers to acute adjustments in body processess that maintain a constant internal environment

homeorhesis inovlves prolonged coordination of an individual's metabolism to prioritize the allocation of nutrients depending on the physiologic status of the individual (ex. pregnancy, lactation, winter etc.)
Term
Where is endogenous somatotropin produced and in response to which physiologic conditions?
Definition

the hypothalamus secretes growth hormone releasing hormone (GHRH) in response to low BG and high levels of circulating amino acids, which stimulates secretion of somatotropin from the anterior pituitary.

 

**** as lactation increases endogenous bST increases

Term
How does somatotropin mediate a physiologic effect? And what is that effect?
Definition
binds to tissue receptors (liver, fat, CMI/HMI, connective tissue, beta islet cells) --> increase release of NEFAs/FFAs from adipose, increase gluconeogenesis in the liver, increases calcium availability from the bones, increases blood flow to the mammary gland (through insulin-like growth factor)
Term
T/F bST has no impact on human growth because its primary structure (amino acid sequence) is NOT homologous with human somatotropin
Definition
TRUE
Term
T/F bST is released from the anterior pituitary in only a single form
Definition

FALSE

 

*** released in 1 of 4 variants, they differ slightly in amino acid sequence and overall length

 

1: 191 aa long, leucine @ position 127

 

2: 191 aa long, valine @ position 127

 

3: 190 aa long, leucine @ position 127 (commercial bST is variant 3)

 

4: 190 aa long, valine @ position 127

Term
T/F when exogenous supplementation of bST is stopped, normal pituitary secretion of endogenous bST resumes within 24 hours
Definition
TRUE
Term
How much can bST (posilac) increase milk production in dairy cows?
Definition
an average of 10 more pounds of milk a day per cow treated with rbST
Term
What are the mechanisms of heat loss?
Definition

increased heat loss -->

 

conduction: lay on a cold surface

convection: wind blows over skin

radiation --> seek shade

evaporation

 

AND

 

decrease heat production --> reduce feed intake

Term
What is a thermal neutral zone?
Definition
ambient temp at which no physiologic/metabolic effort is necessary to regulate body temp

*** very narrow in calves (btwn 10-20 degrees Celsius), more broad in mature cows (more body fat, functioning rumen) <-- because cow can handle cold better than calf, but heat stress occurs at around the same temp regardless of age and size (72 degrees Fahrenheit)
Term
what is the difference between heat stress and heat stroke? What are some risk factors?
Definition
stress --> can adapt
stroke --> no ability to adapt

risk factors --> high ambient temp/humidity, heavy fleece, excessive stress/physical activity, inadequate access to shade or water
Term
What are some consequences of heat stress in cattle?
Definition

decreased dry matter intake --> decreased milk production, increased risk of metabolic disease

 

stress -> increased cortisol --> immunosuppression, reduced fertility (long term effects on eggs and sperm and immediate effects on embryos)

 

musculoskeletal (the cow is standing much more to increase convection cooling) -> clinical lameness 6-8 weeks after heat stress

Term
Heat stroke occurs at what temp in the cow?
Definition
> 170 degrees Fahrenheit

results in DIC and multiorgan failure
Term
What are some mechanisms for preventing heat stress/heat stroke?
Definition
adequate air movement to maintain inside temp the same as outside, adjustable curtains, build the barn to take advantage of prevailing wind direction (in MN east-west orientation) and avoiding obstructions to airflow (ie. hills, trees etc.)

provide multiple waterers, shade in pastures, install fans and sprinkler systems
Term
What is the best bedding for calves in the winter?
Definition
deep dry straw --> nesting score of 3
Term
how can you prevent cold stress in calves?
Definition
increase volume (50-100%) and caloric density of milk (increased fat content)

provide good shelter and bedding (nesting score 3)
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