L29- Endocrine Pathology VII (Ca, PO4, Mg) Flashcards by Connor Patrick

list the normal serum values of the following:

Ca++
PO4-

Ca: 2.2-2.6 mmol/L

PO4: 0.8-1.4 mmol/L

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(1) amount of Ca in body in Kg, predominately in (2) form
50% serum Ca is in (3) form, and the other half is in (4) form
total Ca levels are affected by the concentration of (5)
ionized Ca levels are affected by (6)

1- 1 Kg
2- 98% in bone, hydroxyapatite crystals

3- ionized Ca
4- bound to albumin

5- protein
6- pH (inc ionized Ca with acidosis / low pH —- dec in alkalosis)

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describe general Ca function in ECF

regulates neuromuscular excitability

- acts as co-factor for clotting factors

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describe general Ca function in cells

regulate activity of many enzymes

- exerts 2nd messenger hormonal function

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list the hormones controlling Ca levels

PTH
1,25-dihydroxycholecalciferol (vitD)
calcitonin

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describe role of PTH in Ca metabolism

-responds to low serum Ca (ionized form)

Actions:

bone for Ca/PO4 release
kidney for inc Ca reabsorption, dec PO4 reabsorption
kidney for vitD activation

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describe the role of vitD in Ca metabolism

-activated by liver and kidney

Actions:

enhances Ca/PO4 absorption in the GIT
bone for Ca/PO4 resorption

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describe the role of Calcitonin in Ca metabolism

(not involved??)
????
responds to high serum Ca (ionized)

Actions:

inc osteoblast activity (Ca/PO4 deposition)
dec Ca reabsorption and GIT absorption
dec vitD activation

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list the 2 main causes of hypercalcemia

(90% of all cases)

1) hyperparathyroidism (most common)
2) malignant disease

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list the ‘other’ (not main 2 causes) of hypercalcemia

excess vitD (vitD intoxication)
granulomas (Tb, lymphoma, sarcoidosis –> vitD activation)
high bone turnover: Thyrotoxicosis, Paget’s disease

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Hypercalcemia clinical features:

(1) mainly
(2) renal
(3) MSK

1- asymptomatic (50%)

2- polyuria, stones, nephrocalcinosis (Ca crystal deposition in kidney –> renal failure)

3- muscle weakness; rarely demineralization, subperiosteal bone resorption, bone cysts (osteitis fibrosa cystica)

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Hypercalcemia clinical features:

(1) mainly
(2) neurological
(3) GI

1- asymptomatic (50%)

2- psychiatric / neurological Sxs (MDD, lethargy, seizure)

3- anorexia, constipation, pancreatitis, peptic ulcer

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list primary causes of hyperparathyroidism

solitary adenoma (mainly)

- hyperplasia, carcinoma (rarely)

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describe secondary hyperparathyroidism

rxn of parathyroid glands to hypocalcemia not aused by parathyroid pathology

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describe tertiary hyperparathyroidism

PTH incs to maintain normocalcemia in vitD deficiency
parathyroid hyperplasia occurs
PTH secretion becomes independent of Ca levels

-seen most often in renal failure patients (no vitD activation)

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hyperparathyroidism is prominent component in ______ congenital disorders

MEN1, MEN2 (multiple endocrine neoplasia syndromes)

Parathyroid (adenoma/carcinoma) is more popular and it is (usually/not) functional. Prognosis depends on (3).

1- adenoma
2- functional
3- extent of invasion and presence of metastasis

list the main genes related to parathyroid tumors

MEN1 mutation

- cyclin D1 gene rearrangement

functional adenoma or carcinoma of the parathyroid can be complicated by the following hypercalcemia sequelae

bone resorption

- foci of hemorrhage, necrosis

Parathyroid Adenoma:

gross appearance
histological appearance

Gross:

typically well-circumscribed, soft, tan nodule
invested by delicate capsule
confined to single gland

Microscopy:

predominantly chief cells with rim of compressed non-neoplastic parathyroid tissue separated by fibrous capsule
minimal nuclear pleomorphisms, forming follicle, no anaplasia

Parathyroid Carcinoma:

gross appearance
histological appearance

Gross:

enlarge one of glands
gray-white, irregular mass
dense fibrous capsule

Microscopy:

uniform cells resembling normal cells arranged in nodular / trabecular pattern
only reliable Dx is invasion or metastasis

hypercalcemia investigations

plasma levels of:

Ca++ (total)
PO4-
ALP
PTH

hypercalcemia management

correct dehydration
furosemide
bisphosphates
calcitonin

list the causes of hypocalcemia

hypoalbuminemia: low total plasma Ca, but normal ionized Ca
Chelation by EDTA
PTH related: hypoparathyroidism, pseudohypoparathyroidism, hypomagenesemia
vitD metabolism defect: Ricketts, osteomalcia, CRF, vitD resistant rickets. liver disease, anticonvulsion therapy
acute pancreatitis

list the clinical features of hypocalcemia

- inc neuromuscular excitabiliy --> tetany, paresthesia, muscle cramps - prolonged hypocalcemia, associated with cataract, mental retardation, psychosis, inc intracranial P, seizures

describe hypocalemicia investigation results

-dec serum Ca Primary hypoparathyroidism: dec Ca, dec PTH, inc PO4 VitD deficiency: dec Ca, inc PTH, dec PO4

list the many general causes of hypoparathyroidism

- Congenital absence - Autoimmune syndrome - Thyroidectomy, neck surgery - Pseudohypoparathyroidism

describe associations with congenital absence of parathyroid glands

-isolated OR -DiGeorge --> thymic and congeniral heart defects

autoimmune syndromes causing hypoparathyroidism are usually associated with....

adrenal or ovarian failure (associated with other autoimmune issues)

describe pseudohypoparathyroidism

- dec responsiveness of target organs b/c PTH receptor issue | - sex-linked: males 2x more likely than females

Hypoparathyroidism: - (1) skeletal features - (2) other features

1- short stature, short metacarpals, short metatarsals 2- cataracts, mental retardation, testicular atrophy

list the many hypophosphatemia causes

Reduced absorption / Malabsorption Inc cellular uptake: treated DKA, hyperalimentation alkalosis Inc excretion: hyperparathyroidism, hypomagnesemia, renal tubular defects, dialysis Dilution- volume expansion Chronic alcohol abuse

hypophosphatemia Sxs

- muscle weakness - Hemolysis: due to 2,3-diphosphoglycerate (2,3-DPG) depletion - Respiratory failure: severe hypophosphatemia (critically ill Pts) - Rhabdomyolysis: skeletal muscle breakdown --> Myoglobin release --> ARF

hyperphosphatemia causes

- artefact: hemolysis or delay in separation of blood samples - CRF - hypoparathyroidism

hyperphosphatemia effects

-high plasma Ca, PO4- | => metastatic calcification (Ca salt deposition in normal tissue)

hypomagnesemia: - (1) associations - (2) causes

1- hypocalemia, hypokalemia 2- malabsorption, malnutrition, alcoholism, diuretics, chronic mineralocorticoid excess

hypomagenesemia Sxs

``` tetany agitation ataxia tremors convulsions ```

hypermagenesemia causes

renal failure

hypermagnesemia effects

levels >6mg/L => respiratory paralysis and cardiac arrest