calcium & phos metabolism

7/31/2019 CALCIUM & Phos Metabolism

1/35

Calcium- Phosphorus -

homeostasis

Nirmal Baral MD


2/35

2

Calcium


3/35

3


4/35

4


5/35

5

Regulation of the synthesis of 1,25-DHCC:

Plasma Phosphate activity of 1 hydroxylase.

Plasma Calcium production of PTH activates 1

hydroxylase.Thus

Action of phosphate on kidney 1 hydroxylase is direct


6/35

6


7/35

7

ACTION OF CALCITRIOL ON THE INTESTINE

CALCITRIOL Absorption of Ca & P from GIT

Like steroid hormone Calcitriol + Cytosolic Receptor

[Intestinal cell ]

Calcitriol Receptor Complex

nucleus

mRNA

Calcium Binding Protein

Ca uptake by the intestine


8/35

8

ON BONE:

CALCITRIOL n. & activity of osteoblasts;also secretion of ALP by osteoblasts mineralization of bone

Mineralization of bones

Calcitriol Osteoblast

Ca uptake fordeposition as calcium phosphate.

ON KIDNEY:

Calcitriol excretion and reabsorption of Ca & P plasma Ca & P


9/35

9

Calcitriol also ses renal excretion of Ca S Ca

Net effect =

-+ + ++


10/35

10

Secretion ofPTH is under negative feedback regulation by S Ca

Low S CaPTH secretion

Action of PTH- via cAMP S Ca

1. Action on Bone - demineralization or decalcification of bone byosteoclasts [bone resorption]

S Ca [at the expense of loss of Ca from bone].

Quantitatively most important action.

2. Action on Kidney - Ca reabsorption by DCT S Ca

Most rapid but quantitatively less imp as compared to action on bone

[PTH at PCT ses PO4 reabsorption U excretion S phosphate].

3. Action via Calcitriol - by activation of activity of 1 -hydroxylase on

intestine, bone, kidney S Ca

PTH - parathyroid glands S Ca


11/35

11

Calcitonin- parafollicular cells of ThyroidS Ca

Calcitonin action on calcium is antagonistic to thatofPTH

1. Calcitonin promotes calcification by increasingactivity of osteoblasts [v/s PTH- decalcification]

2. Calcitonin ses bone resorption by osteoclasts[v/s PTH- bone resorption by osteoclasts]

3. Calcitonin ses Ca excretion in urine [v/s PTH- Ca

reabsorption by DCT]

Calcitonin


12/35

12

S CaCalcitonin & PTH

S Ca Calcitonin & PTH

demineralization & effect on kidney & PTH via 1 hydroxylase

S Ca


13/35

13

Low pH

Increased secretion of PTH

Increased urinary excretion of

phosphate

Increased net acid excretion byincreased buffering of excreting

H+ ions

Effect of pH onCalcium/Phosphate Metabolism:

Regulation of PTHSecretion:


14/35

14


15/35

15

HypercalcemiaSymptoms: Polyuria, dehydration, confusion, depression, fatigue,

nausea/vomiting, anorexia, abdominal pain, and renal stones.

Signs: Diminished reflexes, short QT interval on ECG.

Etiologies:1. Increased GI Absorption of Calcium:

Milk-alkali syndrome

Elevated Calcitriol: causes-Vitamin D excess

Chronic granulomatous diseases mc in sarcoidosis, but also in TB &histoplasmosis. Due to calcitriol produced by activated macrophages withingranulomas.

Excessive vitamin D intake Acromegaly (acromegaly + hypercalcemia should suggest MEN I)

Lymphoma

Elevated PTH [by ing 1 -hydroxylase ] Hypophosphatemia [by ing 1 -hydroxylase ]


16/35

16

2. Increased Calcium Loss From Bone: Increased Bone Resorption

Elevated PTH Primary hyperparathyroidism

Adenoma (80% of 1 hyperparathyroidism)

Hyperplasia (15%)

Carcinoma (


17/35

17

3. Decreased Bone Mineralization: Aluminum intoxication seen in end-stage renal disease.

Elevated PTH (see above)

4. Decreased Urinary Calcium Excretion: Thiazide diuretics

Familial hypocalciuric hypercalcemia

Elevated calcitriol (see above)

5. Pseudohypercalcemia(due to increased protein binding ofcalcium in hyperprotiein states)

Severe dehydration (due to concentration of albumin)

Multiple Myeloma

In ambulatory patients, 90% of cases will be due tohyperparathyroidism.

In hospitalized patients, 65% of cases will be due to malignancy.


18/35

18

Diagnosis Phosphate PTH Calcitriol UrinaryCalcium

PrimaryHyperparathyroidism

Variable / Normal

Malignancy Variable / Normal

Vitamin D Excess / Normal

/ Normal

Milk-Alkali Syndrome / Normal / Normal Normal Normal

Granulomatous Disease

/ Normal

Thiazide Diuretics / Normal / Normal Normal


19/35

19

Hypocalcemia

Symptoms: Irritability, muscle cramps, depression, psychosis, bronchospasm, andseizures.

Signs: Increased reflexes, prolonged QT interval on ECG (the only cause of a prolongedQT with a normal duration of the T wave itself)

Chvosteks sign Tapping of the facial nerve induces contractions of the facial muscles Trousseaus sign Inflation of a blood pressure cuff induces carpal spasm

Etiologies:

A. Decreased GI Absorption of Calcium Poor dietary intake of calcium Decreased GI absorption with normal dietary intake

B. Decreased calcitriol1. Vitamin D deficiency Poor dietary intake of vitamin D

Inadequate sunlight exposure- purda, burka etc Malabsorption syndromes Drugs Any drug which increased activity of the P-450 system, increases

inactivation of vitamin D. These include isoniazid, theophylline, rifampin,and most anticonvulsants.

Nephrotic syndrome Due to loss of vitamin D binding protein in the urine


20/35

20

Hypocalcemia cont

2. Decreased conversion of vitamin D to calcitriol Liver failure

Renal failure Low PTH Hyperphosphatemia Vitamin D dependent rickets, type 1 (psuedovitamin D deficient

rickets) AR due to deficiency of 1 hydroxylase.

C. Vitamin D resistanceHereditary vitamin D resistant rickets (formerly called vitamin Ddependent rickets, type 2) A disorder which manifests as end-organresistance to calcitriol, due to mutations in the calcitriol receptor.

D. Increased Bone Mineralization

Low PTH PTH resistance Hungry bones syndrome The rapid mineralization of bones

following parathyroidectomy Osteoblastic metastases seen in patients with metastatic prostate

or breast cancer.

E D d B R ti


21/35

21

E. Decreased Bone Resorption Low PTH PTH resistance Decreased calcitriol

F. Increased Urinary Excretion of Calcium1. Low PTH (hypoparathyroidism)-

a. Post-Thyroidectomy complication (most common cause)b. Post I131 therapy for Graves disease or thyroid cancer

c. Autoimmune hypoparathyroidismi. Isolatedii. Polyglandular Autoimmune Failure, type I a combination of

hypoparathyroidism, Addisons disease, and chronic mucocutaneouscandidiasis

d. Hereditary hypothyroidism

e. Infiltration of the parathyroidi. Hemochromatosisii. Wilsons diseaseiii. Metastatic cancer

f. Congenital hypoparathyroidismi. Autosomal dominant hypocalcemia.ii. DiGeorge Syndrome


22/35

22

2. PTH Resistance (pseudohypoparathyroidism) Aheterogeneous group of disorders characterized by end-organresistance to PTH, classified as types 1a, 1b, 1c, 2, andpseudopseudohypoparathyroidism

3. Deficiency of calcitriol

G. Internal Redistribution

Pancreatitis (due to formation of calcium salts inretroperitoneal fat)

H. Intravascular Binding

Citrate excess from multiple transfusions Citratechelate calcium in the serum, dropping levels of the activeionized form, without affecting total calcium levels.

Acute respiratory alkalosis Elevated pH causes morecalcium to become bound to albumin, also dropping levels ofionized calcium.


23/35

23


24/35

24

Phosphorus Adult body 1 kg

Distribution - 80% in combination with Ca inbones and teeth

- 1% in muscle and blood

- 1% in various chemical compounds

Dietary Requirements: Same as Ca (Adult 800mg)

Ca: P Ratio is 1:1

Sources: Milk, cereals, leafy vegetables, egg, meats, etc.

Excretion: Urine and feces.

Renal threshold for phosphorus 2mg/dl

Ph h


25/35

25

PhosphorusSerum Phosphate= Adult: 3 5 mg/dl; Children: 4.5 to 6.5 mg/dl

Absorption- From Jejunum.- Calcitriol PO4 absorption along with Ca.

plasma Ca & P- Acidity favours while Phytate.

PTH at Kidney PCT

ses PO4 reabsorption U excretion S phosphate

Calcitriol on Kidney excretion and reabsorption of Ca & P plasma Ca & P

PTH on Bone the mobilization of Ca & P plasma Ca & P

NET EFFECT OF PTH ON BONE &KIDNEY IS TO ECF Ca & P


26/35

26

Physiological Functions:

Intracellular functions:- For high energy phosphate (ATP)

- muscle contractility

- neurological functions- electrolyte transport

Constituent of nucleotides enzymes:

NAD, NADP, ADP, AMP.

Hyperphosphatemia


27/35

27

Hyperphosphatemia Symptoms: When they occur, they are usually related to concurrent hypocalcemia.

Etiologies:

1. Increased GI intake Laxative

2. Decreased urinary renal excretiona) Renal Failure (occurs when GFR < 20-25 mL/min)

b) Increased active renal reabsorption of phosphatei. Hypoparathyroidism

ii. Acromegaly

iii.Bisphosphonates

iv. Hyperthyroidism

v. Dehydration

vi. Familial tumoral calcinosis - A rare autosomal recessive disorder characterized byhyperphosphatemia, calcified soft-tissue masses, and normal [Ca+2].

3. Internal Redistributiona) Cell lysis

i. Tumor lysis syndromeii. Rhabdomyolysis

b) Transmembrane shift Metabolic acidosis This results from decreased glycolysis and decreased intracellular

phosphate utilization.

4. Pseudohyperphosphatemia

Multiple Myeloma


28/35

28

Causes of hyperphosphataemia

Chronic renal failure

Phosphate-containing enemas

Tumour lysis

Myeloma-abnormal phosphate-binding

protein

Rhabdomyolysis


29/35

29

Causes of hypophosphataemia

Hypophosphatemia


30/35

30

Hypophosphatemia

Symptoms: Mild symptoms not seen until S phosphate < 2.0 mg/dL.Serious symptoms do not occur until serum phosphate < 1.0 mg/dL.

Symptoms are generally due to one of three mechanisms:

1. Hypophospatemia induces bone resorption. Whenprolonged, this leads to osteomalacia and rickets.

2. Intracellular ATP levels fall, leading to impairment ofmuscle contractility (manifesting as proximal muscleweakness, dysphagia, ileus, respiratory failure, and acuteCHF), metabolic encephalopathy (irritability, paresthesias,confusion, coma), increased RBC rigidity (predisposing to

hemolysis), impaired phagocytosis, and impairedgranulocyte chemotaxis.

3. Red cell 2,3 DPG levels fall, increasing the affinity ofhemoglobin for oxygen, and leading to reduced oxygen

release and tissue ischemia.


31/35

31

The conditions in which symptoms from hypophosphatemia areprimarily seen are alcoholism (from poor intake combined withvitamin D deficiency) and the chronic ingestion of antacids.


32/35

32

Essential Macrominerals: Summary

Elements Functions Metabolism Deficiency Toxicity Sources

Calcium Constituentof bones,teeth;regulationof nerve,musclefunction.

Absorptionrequirescalcium-bindingprotein.Regulatedby vit D,parathyroidhormone,calcitonin,etc.

Children:Rickets.

Adults:Osteomalacia.May contributeto

osteoporosis.

With excessabsorption due tohypervitaminosis Dor hypercalcemiadue tohyperparathyroidism, or idiopathichypercalcemia.

Dairyproducts,beans,leafy veg.

Phosphor

us

Constituentof bones,teeth, ATP,phosphorylatedmetabolicinermediates. Nucleicacids.

Control ofabsorptionunknown (vitD?). Serumlevelsregulated bykidneyreabsorption.

Children:rickets.

Adults:osteomalacia.

Low serum Ca2+PI

ratio stimulatessecondaryhyperparathyroidism; may lead tobone loss.

Phosphatefoodadditives.

Functions Metabolism Deficiency Toxicity Source


33/35

33

Functions Metabolism Deficiency Toxicity Source

Na+ Principal cationin ECF.Regulates plasmavol, acid-base

balance, nerve &muscle function,Na+/K+ - ATPase.

Regulatedbyaldosterone.

Unknown onnormal diet;secondary toinjury or illness

Hypertension(insusceptibleindividuals).

Table salt;salt addedtoprepared

food.

K+ Principal cationin ICF; nerve &muscle function,Na+/K+ - ATPase.

Alsoregulatedbyaldosterone.

Occurs secondaryto illness, injury,or diuretictherapy; muscularweaknessparalysis, mentalconfusion

Cardiacarrest, smallbowel ulcers.

Vegetables, fruit, nuts.

Cl- Fluid & electrolytebalance; gastricfluid; chloride shiftin HCO3- transportin erythrocyts

Infants fed salt-free formula.Secondary tovomiting, diuretictherapy, renaldisease.

Table salt.

Mg++ Constituent ofbones, teeth;enzyme co-factor

(kinases, etc).

Secondary tomalabsorption ordiarrhea,

alcoholism.

Depresseddeep tendonreflexes and

respiration.

Leafygreen veg.(containing

chlorophyll).

E ti l Mi i l


34/35

34

Essential Microminerals:Summary of major characteristics


Cobalt Required only as aconstituent of vitB12.

As for vitamin

B12.

Vit B12 defic. Foods of

animalorigin.

Copper Constituent ofoxidase enzymes:cytochrome coxidase, etc.Cystosolicsuperoxidedismutase. Role iniron absorption.

Transportedby albumin;bound toceruloplasmin.

Anemia(hypochromic,microcytic);secondary tomalnutrition.Menkes

syndrme

Rare;secondaryto Wilsons

disease.

Liver.

Iodine Constituent ofthyroxine,triiodothyronine.

Stored inthyroid asthyroglobulin.

Children:cretinism.Adults: goiterandhypothyroidism, myxedema.

Thyrotoxicocis, goiter. Iodizedsalt, sea-food.



35/35

35

e e ts u ct o s etabo s e c e cy o c ty Sou ces

Iron Constituent ofhemeenzymes(hb,cytochro

mes, etc).

Transported astransferrin;stored asferritin or

hemosiderin;lost insloughed cellsand bybleeding.

Anemia(hypochromic,microcytic).

Siderosis;hereditary

hemochromatosis).

Redmeat,liver,eggs.

Ironcookware.

Zinc Cofactor of

manyenzymes:lactatedehydrogenase, alkalinephosphatase,

carbonicanhydrase,etc.

Hypogonadism,

growth failure,impaired woundhealing,decreased tasteand smell acuity;secondary to

acrodermatitisenteropathica,parenteralnutrition.

Gastroint

estinalirritation,vomiting

Fluoride Increaseshardness ofbones andt th

Dental caries;osteoporosis (?).

Dentalfluorosis.

Drinkingwater.

calcium & phos metabolism

Documents