Hypocalcemia

Clinical Observations for Hypocalcemia/Hypomagnesemia

• Older fresh cows show ataxia or recumbency shortly after calving
• Older fresh cows leak milk after leaving the milking parlor
• Metritis incidence is higher than usual, placenta retention, dystocia, and twinning rates are not higher
• There is an increase in displaced abomasums
• Dairy cows in mid-lactation respond poorly to IV CMPK solutions (Ca, Mg, P, K)
• There have been sudden deaths in beef cows before and after calving

Hypocalcemia (Clinical or Subclinical)

• Decreases skeletal muscle function, leading to an increased risk of injury
• Reduces smooth muscle function, decreasing rumen and abomasal motility, leading to reduced dry matter intake
• Ketosis and metritis can occur
• Milk yield is decreased

Calcium Homeostasis

• Normal blood calcium levels are 8.0-10.0 mg/dL
• Subclinical hypocalcemia (SCHC) range is 5.5-7.9 mg/dL
• Clinical hypocalcemia is less than 5.5 mg/dL, commonly known as milk fever
• Milk fever symptoms include: AFEBRILE, ataxia, flaccid paralysis, and death
• Subclinical issues can co-occur, and the risk increases with age

Timing Considerations for Calcium

• Subclinical hypocalcemia (SCHC) occurs just prior to parturition up to 72 hours post parturition
• Clinical hypocalcemia peaks prior to parturition up to 72 hrs post parturition

Incidence Estimates of Hypocalcemia

• Clinical hypocalcemia affects approximately 5% of older cows and is rare in first lactation animals
• Subclinical hypocalcemia affects approximately 50% of older cows and 25% of first lactation animals
• In USA confinement herds, milk fever impacts 0.7% of first lactation cows, 2% of second lactation cows and 5% of >3 lactation cows
• Subclinical hypocalcemia impacts 25% of first lactation cows, 54% of second lactation cows and 53% of >3 lactation cows

Clinical Hypocalcemia as a Gateway Disease

• Increases the probability of subsequent diseases:
  • 3.4X increase in metritis
  • 16.9X increase in mastitis
  • 7.5X increase in retained placenta
  • 2.5X increase in death

Subclinical Hypocalcemia as a Gateway Disease

• Raises the probability of:
  • 3.7X increase in displaced abomasum
  • 5.5X increase in ketosis
  • 3.4X increase in retained placenta
  • 4.3X increase in metritis

Hypocalcemia Benchmarks

• Intervention is recommended if:

  • 1% clinical hypocalcemia in older cows

  • 25% subclinical hypocalcemia in older cows

  • 12% subclinical hypocalcemia in heifers

Regulation of Calcium Homeostasis

• Regulated by Parathyroid Hormone (PTH)
• PTH responds to minute changes in blood calcium (Ca) concentration
• Decreased Ca triggers increased PTH

Parathyroid Hormone (PTH) Action

• Bone:
  • PTH stimulates osteoclast recruitment & activation
  • Results in ~9-15 g Ca being released from bone fluid
• Kidney:
  • PTH leads to 25-OH vit D conversion into 1,25(OH)₂D
• Gut:
  • 1,25(OH)₂D conversion stimulates active mobilization of 45-150 g Dietary Ca intake
• Lactation exports around: 20-30 g Ca
  • Colostrum removes 2-2.3 g Ca lost per kg
  • Milk removes 1.1 g Ca lost per Kg
• Extracellular Ca pool is: ~11 g
  • serum Ca is about ~ 3.5 g
• Ca excreted via: 0.2 - 6 g Urine and Endogenous Fecal Loss: 5-8 g

Role of Magnesium in Calcium Homeostasis

• The normal pH is 7.35, and there should be normal magnesium levels
• Parathyroid Hormone (PTH) is released in response to hypocalcemia
• PTH interacts tightly with receptors on kidney and bone
• Cyclic AMP is produced
• Effective Ca bone resorption & renal production of 1,25 dihydroxyvitamin D along with enhanced Ca dietary absorption

Calculating Dietary Cation Anion Difference (DCAD)

• Dietary cations minus dietary anions = DCAD
• Major cations: Sodium (Na) and Potassium (K)
• Major anions: Sulfur (S) and Chlorine (Cl)
• Negative DCAD indicates more anions than cations
• Positive DCAD indicates more cations than anions

Dietary Cation-Anion and Acid Idea

• Derived from strong ion difference theory of acid-base balance

Hypocalcemia and its Association with Alkalosis and Hypomagnesemia

• Hypocalcemia: Is a direct result of metabolic alkalosis due to a positive DCAD diet primarily from dietary K (also Na)
• Hypocalcemia: Can occur secondarily to hypomagnesemia

Impact of Metabolic Alkalosis on PTH

• With metabolic alkalosis and normal magnesium, the Parathyroid Hormone (PTH) released in response to hypocalcemia is less able to recognize and bind to receptors
• Ca bone resorption & renal production of 1,2 dihydroxyvitamin D is impaired which makes Ca dietary absorption less effective

Impact of Hypomagnesemia on PTH

• With normal pH, 7.35, hypomagnesemia blunts PTH ability to produce C-AMP
• Results in less effective Ca bone resorption and reduced renal production of 1,2 dihydroxyvitamin D

Hypocalcemia Prevention Methods

• Minimize pre-calving dietary calcium to <20 gms/day but it is almost impossible to balance a ration at this low level
• Zeolite as a dietary supplement with synthetic aluminum silicate that binds Ca, Mg, and P in the rumen which reduces absorption but proper Mg dietary level is very important
• Injectable Vitamin D daily injections >10 days to 30 days before calving, this Hypocalcemia prevention level is at or close to Vit D toxic level. Not recommended
• Balance diet with cation anion difference (DCAD) for <1.0% to 1.5% K on dry matter basis and Mg level to 0.40% with a Goal: DCAD = 0 to + 10 mEq/100gm

Diet DCAD Adjustment

• Nutritional software programs calculate DCAD using the DCAD calculation (Na+ + K+) – (S¯¯ + Cl-) = mEq/100gm
• Some software programs use mEq/kg mEq/100gm = (milligrams X valence)/g atomic weight
• Sulfur has a valence of 2 while all others are 1
• Ie: If diet is 0.2% Cl or 200mg Cl/100 gm then, mEq Cl = 200 mg X 1valence/35.5 = 56 mEq Cl

DCAD steps to prevents clinical and subclinical cases

• Balance diet <1.0 to 1.5% K on dry matter basis, set dietary Mg at 0.4%
• Regulate diet and achieve a negative DCAD by adding anions (S-- & Cl-) to the diet to slightly acidify the cow
  • Chloride is 6X times more acidifying compared to S-
  • Achieve Goal: DCAD = -15 to 0 mEq/100gm
  • Balance diet for 0.25% Phosphorus - <35 grams per day to improve calcium homeostasis

Clinical and subclinical prevention method

• Feed negative DCAD diet at least: 10-21 days prior to calving
• Acidification will occur within about 3-5 days
• Can feed for the entire dry period (45-60 days)
• It is not necessary to feed 1st lactation animals -DCAD diet but it does help reduce the amount of udder edema

Commercial DCAD Products

• SoychlorⓇ is Hydrochloric acid, CaCl, at 1.5-2.5 lbs./head/day: 22.4% CP: no NPN
• BiochlorⓇ is MgCl 2.0 to 2.5 lbs./head/day with 48% protein: some NPN

Cautions when Adding DCAD

• Because Na is a cation and salt (NaCl) is mistakenly/purposely is left out of the diet then NaCl will not contribute to DCAD due to containing both + and - charge
• Indicator that NaCl is deficient: Pica
• Do not use Sodium bicarbonate in pre-calving pen, it is a + charge only

Management for Monitoring DCAD

• Measuring Urine pH: Mid-stream catch (devoid of manure) with either pH paper or pH meter with a Goal to achieve a mean urine pH between 6.2 to 6.8 (6.5 to 7.0)
  • Normal pH (not on DCAD) is 7.8-8.2
• Sample from a minimum of 8-12 cows that need to have been on the DCAD diet for at least 3 days
• Average pH = 6.4 for both herds however, it is important to look at the distribution of pH values: must also look at the distribution of pH values

DCAD Management Considerations

• A urine pH that indicates over acidification is a pH ≤5.5 . It is considered uncompensated metabolic acidosis and means very poor fresh cow health
• Cows start lactation very, very poorly and indications include: low dry matter intake, low production, and death

Alternative Hypocalcemia Prevention Feed Product

• Use Zeolite (10 g zeolite binds 1 g Ca) to reduce available diet Ca level leading to the stimulation of PTH and also binds P and Mg through transient reduction of blood Mg and P
• Can be easier to manage than DCAD

Assessing Calcium Homeostasis Through Serology

• Assess serum Ca and Mg serum 12-24 hours post-calving (nadir)
• Test 12-15 animals (choose "normal" animals)
• ≥20% of samples < concern level = diagnosis

Concern levels for Ca and Mg

• Ca: 8.0 mg/dL
• Mg: 2.0 mg/dL

Down or Ataxic Cows Assessment

• Always assess Ca and Mg together
  • Primary Ca issue = Mg will be normal
  • For a secondary Ca issue = Mg will be below 2.0 mg/dL
• Hypocalcemia cases where P will almost always be low
  • P levels follow Ca levels after treatment

Continued Hypophosphatemia after Ca treatment

• Note: P in IV CMPK is NOT utilized by the cow as it contains sodium hypophosphite
• Treatment for Hypophosphatemia is either:
  • Oral P source: using monocalcium phosphate or dicalcium phosphate
  • IV Fleet® Enema using monosodium phosphate

Hypocalcemia treatments

• Oral: For animals that are still standing and have a swallow reflex
  • Oral treatment shouldn't be attempted in moribund animals due to = aspiration pneumonia
  • Has a lag time and is effective ~ 30 minutes after administration
• Oral prevention measures: Oral calcium gel/bolus at calving and repeat 24 hours later
  • 50 to 250 gms of calcium is a recommended dose

  • 250 gram of soluble calcium may be lethal

• Subcutaneous (SQ): Use CMPK if not severely hypocalcemic or dehydrated
  • Do NOT use solutions containing glucose SQ as it is likely to result in subcutaneous abscesses
  • Effective ~ 30 minutes after administration, blood calcium returns baseline about 6 hours later
• Intravenous (IV): Using IV calcium, jugular only, with recumbent animals, slowly give 500 ml CMPK as more is not needed, can give an additional 500 ml SQ to possibly reduces relapses
• Auscultate during administration: reduce or stop flow rate if arrhythmias occur

Magnesium Homeostasis

• Unlike bone Ca and P, There is no effective, available Mg storage pool
• Dependent on daily dietary intake & solubility

Hypomagnesemia in Dairy Cows

• Serum Mg at treatment after 18 down &/or ataxic cows: 80 to 120 days in milk
• 13 dairy cows responded to IV Ca, Mg, P, K (CMPK®) First 10 samples tested: all levels between 0.2 mg/dL- 1.2 mg/dL
• Diet formulation mistake (contained ½ as much Mg as required)

Hypomagnesemia in Beef Cows

• Pasture hypomagnesemia, grass tetany
• Excessive dietary K levels (rapidly growing grass),
• Reduced dietary Na level
• Sub-optimal Mg consumption
• K reduces active ruminal Mg transport
• Prevention: feed "high Mg” mineral: 12%-14% magnesium to drive Mg across rumen wall regardless of K level (passive transport)
• Winter tetany considerations include high forage diets, Improper diet and/or inadequate mineral Mg consumption and Age due to older animals less able to absorb Mg

Concerns for Magnesium Quality

• The magnesium oxide contained in the mineral supplement is poor where the coarsely processed product is i.e.: Particle coarseness/size reduces magnesium bioavailability
• Must use the pure Mag oxide product going into the product and avoid testing on mineral packs

Mg oxide solubility test

• Add 40 ml, 5% acetic acid (white vinegar) SLOWLY to 3 gm of MgOx, close lid and shake very well then, Let sit for 30 minutes
• Vinegar pH is ~2.4 however, high quality MgOx will increase the pH to ~8.2 while low quality MgOx will slightly increase pH to ~3.8

Treatment for Grass Tetany (Mg)

• Use IV calcium/magnesium/potassium in recumbent animals
• Use CMPK: 500 ml SLOWLY with caution as patients respond very quickly, and can still be very dangerous
• Have an escape plan in place before you remove the halter!!