8. large animal med- disorders of mineral metabolism

what is calcium used for in the body?

-neuronal transmission

-muscular contraction

-hemostasis

-skeletal strength

-fetal skeletal growth

-milk production

what do the most visible disorders of calcium metabolism relate to?

relate to importance in:

-stabilizing the resting potential of nerves

-allowing release of ACh at the NMJs

-and flowing into myocytes to affect a contraction

why is smooth muscle more dependent on calcium than skeletal muscle for contractility?

bc smooth muscle has a poorly developed sarcoplasmic reticulum for calcium storage

where is most of the body's calcium stored?

in bone and teeth (99%)

only 1% is stored in ECF

how much calcium in the plasma is free/active?

50% of plasma calcium is ionized (free, active)

-40% is protein bound

-10% is complexed

which homeostatic mechanisms within the body work to increase plasma ionized calcium?

PTH and 1,25 dihydroxyvitamin D increase ionized Ca by:

-increasing bone resorption

-intestinal uptake

-renal tubular resorption

which homeostatic mechanisms within the body work against PTH/vitD to decrease plasma ionized calcium?

calcitonin

how much calcium per day does a prepartum cow require?

about 40g of calcium per day

how do calcium requirements change with the onset of lactation in dairy cows?

daily requirement abruptly increases by over 100% with onset of lactation

how much calcium is in cow colostrum and milk?

colostrum: 2.3g/L of calcium

milk: 1.2g/L of calcium

how much colostrum/milk do cows make per day?

cows usually makes 16 pounds of colostrum, and 30-60+ pounds of milk

what is periparturient hypocalcemia (milk fever)?

in lactating cows, if the plasma calcium pool is not rapidly replenished thru bone resorption/gut absorption to maintain homeostasis, causes a precipitous drop in plasma calcium

what are causes of periparturient hypocalcemia (milk fever)?

1. high milk production

2. overproduction of calcitonin

3. underproduction of PTH or vitD

4. delayed vitD production

5. slow response of target tissues to PTH and vitD

6. decreased bone remodeling in older animals (more likely, worsens with age)

7. PTHrp from udder surpasses homeostatic mechanisms

bolded/underlined= most commonly/likely

which breeds are at the highest risk of developing milk fever?

mature (4+ years), high producing cows of certain breeds, especially jerseys and guernseys (channel island breeds)

what are the categories of clinical signs of milk fever?

subclinical and clinical stages

what are the clinical signs of the subclinical stage a result of with milk fever?

subclinical signs are due to smooth muscle effects:

-these signs occur before skeletal muscle signs, or may be the only signs

-smooth muscle signs appear first bc smooth muscle more reliant on calcium in blood since no sarcoplasmic reticulum

what is the importance of the subclinical stage seen with milk fever?

subclinical signs can progress to clinical signs and contribute to other disorders

what are clinical signs of the subclinical stage of milk fever?

1. poor uterine muscular contractions

-prepartum: dystocia

-post-partum: uterine prolapse, RFM, metritis

2. poor rumen motility (ileus, bloat, poor appetite, ketosis)

3. poor GI tone and motility, ileus, DA, cecal dilatation and volvulus

4. poor bladder contractility

what is the clinical stage of milk fever?

progression of stages (blend into each other, will see peripheral nerve and skeletal muscle effects)

what clinical signs are seen with the 1st phase of the clinical stage of milk fever?

excitement, tetany, nervousness, tachycardia

-subtle and transient signs, often not noticed

-destabilization of resting potential of nerves

-decreased cardiac contractility

this phase lasts 1-2 hours

what clinical signs are seen with the 2nd phase of the clinical stage of milk fever?

sternal recumbency with flaccid paralysis and depression

-classic milk fever

-dull, poor response to external stimuli

-metabolic neck w/ 'S' curve

what clinical signs are seen with the 3rd phase of the clinical stage of milk fever?

lateral recumbency, coma, death (usually within 24 hours of recumbency)

in cows with milk fever, is their heart rate usually increased or decreased?

due to decreased contractility of the heart, the HR increases

however, in severely affected cows, the HR may actually be slow

when does hypocalcemia/milk fever most commonly occur?

over 80% of cases occur within 24 hours of calving (usually after calving)

how is milk fever diagnosed?

-history

-herd history

-clinical signs

-r/o other causes of dull/depressed cows and bright/alert down cows

what are general causes of dull/depressed cows vs bright/alert down cows?

dull/depressed cows: toxemia/septicemia (endotoxic metritis/mastitis), GI obstruction

bright/alert down cows: musculoskeletal or neurologic condition

what clinpath abnormalities are seen with milk fever?

-low total and ionized calcium

-low phosphate (PO4)

-high magnesium

-stress responses (leukogram, glucose)

what clinpath abnormalities are poor prognostic indicators?

evidence of poor perfusion (metabolic acidosis, high anion gap, hyperkalemia) or severe muscle trauma (high CK, AST) are bad signs

how is milk fever treated?

calculate calcium deficit and replace

w/ 23% calcium gluconate- each bottle contains 10.6g calcium, which is usually sufficient for severely hypocalcemic cow (have to give slowly and monitor HR)

how quickly should milk fever cows respond to IV calcium administration?

improvement should be seen during and after calcium administration

what signs of improvement may be seen in response to treatment with milk fever?

cows become more aware, eructate, defecate, urinate

may try to stand up/run away

how is milk fever prevented?

1. reduction of prepartum calcium intake (old theory)

2. dietary cation-anion difference (DCAD)

3. dont dry cows off

4. vitamins and hormones (not very effective)

5. calcium supplementation w/ oral CaCl gels

6. reduce dietary Ca absorption to increase mobilization by feeding zeolite

bolded= emphasized

how can DCAD prevent milk fever?

by feeding anionic (preferably chloride) salts for last 3 wks of dry period, in conjunction with high calcium diets

absorption of strong ions cause metabolic acidosis, in which acidosis leads to increased bone mobilization (bone is a buffer)

what is the importance of prevention of milk fever?

cows w/ milk fever lose about 14% of the potential production for that lactation (important for dz and complications)

also, cows w/ both clinical and subclinical dz are more likely to develop many other postpartum dz's (RFMs, ketosis, LDA, mastitis, MSK injuries)

what are causes of hypocalcemia in other ruminants (sheep, goats, beef cows)?

when calcium drain is high (late pregnancy, lactation) and calcium intake is deficient

when is hypocalcemia most commonly seen in small ruminants?

dams carrying multiple fetuses (goats, sheep) more likely to develop hypoCa during pregnancy

animals which milk heavily (dairy goats and sheep) more likely to develop hypoCa postpartum

what are clinical signs of hypocalcemia in small ruminants?

similar to cattle with milk fever, but can also see tetany (not just flaccid)

what is non-parturient hypocalcemia often accompanied by in small ruminants?

hypomagnesium (opposite in milk fever cows - hypoca & HYPERMg)

what are 3 clinical disorders associated with hypercalcemia?

1. iatrogenic hypercalcemia

2. neoplasia

3. hypervitaminosis D

what is the most common cause of acute, severe hypercalcemia in ruminants?

IV calcium administration

what can acute hypercalcemia in ruminants result in?

-atrial fibrillation

-cardiac asystole

-polyuria

-excitability

which neoplasias in horses can cause development of hypercalcemia?

lymphoma, gastric squamous cell carcinoma

what causes hypercalcemia in horses with lymphoma/other neoplasms?

may be due to production of PTHrp and bone invasion of the tumor (uncommon in cattle)

what can chronic hypercalcemia lead to?

due to mineralization of tissues:

-lameness

-kyphosis

-dyspnea

-polyuria

how can hypervitaminosis D lead to hypercalcemia?

can occur as a feeding accident in ruminants, or with overzealous supplementation to prevent milk fever or rickets

can also be due to ingestion of plants containing a vitD analogue (overrides homeostatic control of calcium absorption)

which plants contain vitD analogues that when eaten, can lead to hypercalcemia?

-cestrum diurnum

-solanum malacoxylon or sodomaeum

-tricetum flavascens

toxic sun plants

what pathology can hypervitaminosis D (causing hyperCa) lead to?

dystrophic mineralization of tissues

what is the function of phosphorus in the body?

used for intracellular energy (ATP)

how is phosphorus regulated within the body?

affected by mechanisms of calcium homeostasis, but phosphate itself is poorly regulated

in general, mechanisms which increase plasma calcium also increase plasma phosphate (exception is renal resorption, where PO4 is usually lost by the kidney when calcium is conserved)

what is the most common route of phosphorus excretion in most mammals?

urinary loss

where do ruminants mostly excrete/lose phosphorus?

rapidly via salivary secretions (this loss is accelerated by PTH)

what is the consequence of decreased salivation in ruminants?

hyperphosphatemia

what are 3 clinical disorders associated with hypophosphatemia?

1. postparturient hemoglobinuria

2. downer cows

3. rickets

what is postparturient hemoglobinuria?

cows within the 1st month postpartum develop severe IV hemolysis w/ hemoglobinemia and hemoglobinuria

what may postparturient hemoglobinuria correlate to in north america and new zealand?

NA: severe hypophosphatemia

NZ: copper deficiency

what is the pathophys of hypophosphatemia causing IV hemolysis?

hypoP may increase the osmotic fragility of erythrocytes thru ATP deficiency and impaired Na/K pump activity

what are clinical signs of postparturient hemoglobinuria?

- w/ severe and persistent hemolysis, cows become anemic, pale, weak, tachycardic, and recumbent

-severe drop in milk production

-often mild fever

-icterus 3-5 days later

-most severely affected cows die

how is postparturient hemoglobinuria treated?

-blood transfusion and tx w/ sodium acid phosphate

-crystalloid fluids if blood not available

-correction of phosphorus deficiency

-elimination of plant toxins from diet

what are downer cows?

cows with milk fever are usually hypophosphatemic, bc phosphorus is also in high concentrations in milk

most cows respond to calcium tx w/o PO4 supplementation

issue: PO4 is important for intracellular energy and a plasma anion, so hypoP may play a role in relapsing or non-responsive milk fever cows

how are downer cows with hypophosphatemia treated?

give phosphate enemas rectally, orally, or in extreme cases IV

-->these are much more effective at increasing blood phosphorus than IV CMPK; of which is poorly bioavailable

what is rickets?

abnormal proliferation of osteoclasts at the growth plate due to mineral imbalances in young growing animals

what are the consequences of rickets in young, growing animals?

lameness, stunted growth, angular limb deformities

which animals are most susceptible to developing rickets?

-sheep w/ heavy fleece coats

-young cattle in the winter

suspected that vitD deficiency during cloudy winter months, thick hair coats, and dark coat color contribute to rickets

how is a diagnosis of rickets confirmed?

by measuring blood vitamin D

what is seen on radiographs of animals with rickets?

widening and thickening of growth plates, esp around carpus

vertebral body abnormalities may occur as well

how is rickets corrected?

early dietary supplementation or vitamin D shots can lead to correction or cessation of progression of problem

what clinical disorder is associated with high dietary phosphorus?

nutritional hyperparathyroidism

what causes nutritional hyperparathyroidism in horses?

seen in young growing horses or older pregnant mares fed rations very high in phosphorus and relatively deficient in calcium (cereal grains, bran)--> 2nd hyperPTH occurs resulting in remodeling of bone to mobilize calcium (leaves a soft, fibrous skeleton)

aka bran dz or big head

what are clinical signs of nutritional hyperparathyroidism?

-shifting leg lameness

-gait abnormalities

-difficulty masticating

-bilateral facial swelling

what are clinical signs of nutritional hyperparathyroidism due to?

due to:

-crushing injury

-microfractures

-avulsion of ligamentous and tendinous attachments

-proliferative remodeling of bone

how is nutritional hyperparathyroidism diagnosed?

serum mineral concentrations may be normal, but urinary fractional excretions and ration analysis will aid in diagnosis

how is nutritional hyperparathyroidism treated?

dietary modification will lead to resolution of some signs (but bony swelling may persist)

what is the function of magnesium in the body?

important for:

-bone formation

-intracellular enzyme function

-acetylcholin esterase function

-extracellular Mg help maintain resting potential of nerves

where is magnesium absorbed in ruminants?

absorption is highly energy dependent

in ruminants, absorption of Mg occurs mostly thru rumen wall

what is the main source of replenishment of extracellular magnesium?

dietary intake is the main source (very little thru resorption of bone)

what do ruminants depend on for maintenance of magnesium homeostasis?

dietary magnesium

which feed sources is magnesium usually found in adequate concentrations for ruminants?

adequate Mg concentrations seen in most legumes

less adequate concentrations in grasses and cereal crops

which plant sources usually have very low magnesium concentrations?

rapidly growing, lush grass in cool climates, as well as grasses from heavily fertilized pastures

what are clinical disorders associated with hypomagnesemia?

1. grass tetany

2. milk tetany

3. lactation tetany

4. transportation tetany

bolded disorders

consumption of which feed sources leads to grass tetany?

lush, green forage

what causes milk tetany?

milk-fed calves with rumen maturation (milk contains low amounts of magnesium)

what causes lactation tetarny?

seen more in small ruminants than cattle, due to a combination of insufficient intake with lactational drain

what is transport tetany?

most common in young, growing ruminants (esp sheep going to feedlots) who may depositing large amounts of Mg into bone

role of transport likely related to stressful exertion w/ urinary Mg loss and unavailable food for a period of time

what are common clinical signs of disorders associated with hypomagnesemia?

-hyper-responsiveness to stimuli

-flightliness

-muscle fasciculations

-aggressiveness

-hyperthermia due to extreme muscular activity

most ruminants with hypoMg also have concurrent hypo__

hypoCa

what are important diagnostic rule outs for disorders of hypomagnesemia?

nervous ketosis and rabies

how is hypomagnesemia treated?

polyelectrolyte solution containing both Mg and Ca (CMPK)

why is blood measurement of potassium a poor indicator of whole body potassium concentration?

bc potassium is mainly found in the intracellular space

what is hypokalemia syndrome?

treatment of periparturient cows with steroids promoting renal potassium excretion

what does extracellular hypokalemia in hypokalemia syndrome reflect?

severe intracellular deficit

how do cows with hypokalemia syndrome appear?

down, depressed, with metabolic neck ('s' curve)

also have characteristic muscular degeneration of intercostal muscles and diaphragm

how is hypokalemia syndrome treated?

buckets of oral and possibly IV potassium chloride (carefully w/o stopping heart)

how is true hypokalemia diagnosed?

via histo

finding hypoK+ is not enough to confirm