Bone Pathology and related mineral abnormalities

Case Study

AmirReza Dehghanian M.D. APCP

Assistant Professor of Surgical and Clinical Pathology

Shiraz Medical School

Slide 1.1

Slide 1.2

Slide 1.3

Slide 1.4

Slide 1.5

Slide 1.5

Slide 1.7

Normal Values

Ca 8.8 - 10.3 mg/dL

PO4 2.8 - 4.5 mg/dL

Mg 1.7 - 2.2 mg/dl

Cr 0.6- 1.3 mg/dL

BUN 8 - 12 mg/dL

Alb 3.5 - 4.5 mg/dL

TSH 0.3 - 5.0 mIU/ml

iPTH 10 - 65 pg/ml

Case 2

• 40 y/o male is visited for screening puposes. He has no complaints.
• PMHx is negative
• Baseline laboratory studies are significant for serum calcium of 11.5 mg/dL
• Physical examination is normal

Case2: Questions

• What is the most common cause of asymptomatic hypercalcemia?
• This patient’s iPTH would be

a. High

b. Normal

c. Low

• This patient’s PO4 would be

a. High

b. Normal

c. Low

Calcium

• Calcium: - 5^th most common element

- the most prevalent cation

• 99% of total body calcium resides in bone
• 1% in the extracellular fluid (ECF)
• Free ionized calcium: 50%
• physiologically active form, regulated by vitamin D and PTH
• Plasma protein-bound calcium :40%
• 80% associated with albumin
• Complexed calcium :10%
• bound tightly to a variety of anions, including bicarbonate, lactate, phosphate, and citrate

Calcium

• The amount of Ca is balance among intake, storage, and excretion.
• This balance is controlled by transfer of Ca among 3 organs: Intestine, Bone, Kidneys
• Ca ions in extracellular and cellular fluids is essential to normal function of a host of biochemical processes
• Neuoromuscular excitability and signal transduction
• Blood coagulation
• Hormonal secretion
• Enzymatic regulation
• Neuron excitation

Calcium

• Average dietary intake of calcium: 600–800 mg/day
• Less than half of dietary calcium is absorbed in adults
• Absorption: in the duodenum and upper jejunum
• The major stimulus to calcium absorption is vitamin D
• Enhanced by:
• Growth hormone
• Acid medium in the intestines
• Increased dietary protein
• Inhibit by:
• The ratio of ca/ph in the intestinal contents, Ratio >2 / 1, form insoluble calcium phosphates
• Phytic acid, derived from various cereal grains, dietary oxalate and fatty acids, form insoluble calcium compounds

Calcium

• Three principal hormones regulate Ca²⁺ and three organs that function in Ca²⁺ homeostasis
• Parathyroid hormone (PTH)
• 1,25-dihydroxy Vitamin D3 (Vitamin D3)
• Calcitonin
• The principal target organs of these hormones are bone, kidney and intestine

Parathyroid Hormone

Decreased serum calcium stimulates PTH secretion within seconds

Renal effects

• Increase calcium reabsorption and increased phosphorus excretion from renal tubule
• Stimulates renal 1-alpha-hydroxylase to activate vitamin D

Bone effects

• Stimulates bone reabsorption

Net effect

• Increase serum calcium, decrease serum phosphorus

Calcium

Reference Interval

• Normal adults : 8.8 - 10.3 mg/dL
• Serum is the preferred specimen
• Factors that interfere:
• Hemolysis, Icterus, Lipemia, Paraproteins, & Magnesium
• The reference interval for urinary calcium varies with diet
• Individuals on an average diet excrete up to 300 mg/day

Calcium

Analytic Techniques

• The total calcium measurement is easier to perform in the laboratory, but this result must be interpreted in clinical context.
• Role of Albumin:
• In Low albumin states, for example, patients with malignancies, total serum calcium may appear low while ionized calcium is again not very affected

Corrected Calcium

​

​

Total Ca²⁺= serum Ca^{2+ (measured)} +

0.8 x [normal alb-patient alb]

An albumin of about 4.4 is typically used as the normal value

​

Hypercalcemia - Symptoms

• Depend on Calcium level, rapidity of onset, state of hydration
• Most common presentation: Asymptomatic
• Most develop symptoms at a level > 12mg/dL, virtually all symptomatic > 14
• Vague symptoms: fatigue, weakness, anorexia, nausea, polyuria, dehydration, lethargy, stupor, coma

Causes of Hypercalcemia

• Differential diagnosis of hypercalcemia

Increased PTH production

Production of PTH-like hormone

Production of Vit D-like factors

Drugs

Familial disorders

Diseases affecting calcium metabolism

Hypercalcemia: Elevated PTH

• Primary Hyperparathyroidism
• Most common cause of hypercalcemia

(in ambulatory patients)

• Patients usually > 50 years of age
• Females > males ,2 : 1
• Primary elevation of PTH:

85% parathyroid adenoma

10% parathyroid hyperplasia

2% parathyroid carcinoma

​

Hyperparathyroidism

Secondary

• Results from physiologic or pathophysiologic response to hypocalcemia
• When there is resistance to the metabolic actions of PTH
• Most cases due to chronic renal failure – decreased production of activated vitamin D
• Can result from vitamin D deficiency or decreased calcium intake(dietary or malabsorption)

Hyperparathyroidism

Tertiary

• Due to prolonged hypocalcemia (usually due to chronic renal failure)
• This results in parathyroid gland hyperplasia
• May need parathyroidectomy

Hypercalcemia: Other causes

• PTH-related peptide (cancers)

Breast, lung, renal

Thyroid

Lymphoma, Leukemia, Myeloma

• Vit-D3-like factors (granulomatous dx)

TB

Histoplasmosis

Sarcoidosis

Hypercalcemia: Other Causes

• Drugs

Lithium

Antacids

Calcium

Thiazides

Vit-D intoxication

​

Case 3

• 60 y/o old male presents with complaints of fatigue and weakness over 1 month.
• PMHx: Negative
• PE: significant for memory and cognitive defects
• Lab: Ca 15.0 mg/dL

PO4 2.3 mg/dL

Case 2, Questions

• Predict the iPTH values if this patient’s hypercalcemia was due to:

a. Primary hyperparathyroidism

b. Malignancy

c. Vit D intoxication

d. Granulomatous disease

e. Hyperthyroidism