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Laboratory Assessment Of Metabolic Disorders
1. BY
PROF. MOUSTAFA RIZK
PROF. OF CLINICAL PATHOLOGY
FACULTY OF MEDICINE, UNIVERSITY OF ALEXANDRIA.
Laboratory Assessment Of
Metabolic Disorders
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3. When food is ingested there is a parallel rise in blood
glucose level. This increase in blood glucose is
sensed by the ß-cells in the pancreas and as a result,
insulin is secreted.
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5. Insulin circulates through the body and signals to
the major insulin sensitive organs: muscle, liver
and fat to increase their glucose intake . Insulin
simultaneously leads to a reduction of glucose
production from the liver and other organs . In this
way the hormone insulin counteracts the rise of
glucose in the blood returning the system to its
equilibrium.
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30. 30
Selection of patients for
investigations
CHD & vascular disease
Family history of coronary disease
Risk factors for CHD
Clinical features of hyperlipideamia
Lipeamic plasma
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Blood sampling for lipid studies
Serum or plasma
12-14 h fasting for TG,HDL & LDL
Fasting or no fasting for total cholesterol
Usual diet for 2 weeks
Avoid vigorous exercise for 1 day
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Serum Cholesterol 140-200 mg/dL
Serum Triglycerides: 50-159 mg/dL.
HDL-C 35-80 mg/dL
<35 High risk, > 60 Low risk
LDL-C up to 130 mg/dL
< 130 Low risk, >160 High risk
HDL/ Total cholesterol
>26% Low risk, < 16 % High risk
LDL/HDL
> 5% High risk, < 3 % Low risk
Total lipids up to 550 mg/dL.
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34. VALUE OF LIPOGRAM
Increased band Patterns
Chylomicrons I
Beta and pre-beta IIb
Broad beta III
Pre-beta IV
Pre-beta and chylomicrons V
Fredrickson DS. Circulation 1975; 51: 209-211.
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40. Patterns of Serum Protein Electrophoresis
Alb A1 A2 B Gamma
Chronic N,D N,E E N E
infalmmatory
respnce
Acute N,D E E N N,D
inflammatory
respnce
SubacuteN,D N E N N
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43. Patterns of Serum Protein Electrophoresis
Alb A1 A2 B Gamma
Hepatic D N N,D bridging
cirrhosis
Monoclo N,E N,D N N M spike
gammopathy
Monoclo N,E N,D N M spike N,D
gammopathy
Biclonal N,E N,D N M spike M spi
gammopathy
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47. Minerals important in our body includeMinerals important in our body include ::
1- Calcium1- Calcium
2- Phosphorus2- Phosphorus
3- Magnesium3- Magnesium
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50. 11.Parathyroid Hormone:.Parathyroid Hormone:
(A)(A)Synthesis and Secretion :Synthesis and Secretion :
PTH is synthesized and secreted by the fourPTH is synthesized and secreted by the four
parathyroid glands located on the thyroidparathyroid glands located on the thyroid
capsule.capsule.
The conc. of free calcium in blood or extra-The conc. of free calcium in blood or extra-
cellular fluid is the primary regulator of PTHcellular fluid is the primary regulator of PTH
synthesis and secretion.synthesis and secretion.
Magnesium and 1,25(OH)2 D has a minorMagnesium and 1,25(OH)2 D has a minor
influence.influence.
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51. (B) Biological Action :Biological Action :
PTH increases total and free Ca++,
decreases
plasma Ph and increases urinary excretion of
inorganic Ph.
On bones:-
PTH stimulates bone resorption or bone
formation.
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52. 3) In the kidney, PTH :
Increases Ca++
reabsorption in the D.C.T.
Decreases reabsorption of Ph by proximal T.
Inhibits Na+
- H+
antiporter activity which
favors a mild hypercholermic metabolic
acidosis in hyperparathyroid states.
Induces 25-hydroxyvit.D – 1α hydrolase,
increasing the production of 1,25(OH)2D
which stimulates intestinal absorption of both
Calcium and Phosphate.
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56. (C) Clinical Significance :(C) Clinical Significance :
Determination of PTH is useful :
In the D.D. of both hypocalcaemia &
hypercalcaemia.
For assessing parathyroid function in renal
failure.
For evaluating parathyroid function in bone
and mineral disorders.
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58. 22.Vit. D & its metabolites.Vit. D & its metabolites::
(A)(A) Synthesis :Synthesis :
Vit. D is produced endogenously by exposure of
skin to sunlight and is absorbed from food.
It is then metabolized to its main circulatory
form, 25-hydroxyvit. D and then to its
biologically active form, 1,25(OH)2D which is
the hormone regulating calcium and phosphate
metabolism.
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59. Vit. D & its metabolitesVit. D & its metabolites
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60. Vit. D & its metabolitesVit. D & its metabolites
(B) Biological Actions of 1,25(OH)(B) Biological Actions of 1,25(OH)22 D :D :
Ca and ph. concentrations in serum are maintained
by the actions of 1,25(OH)2D on :
1.intestine.
2.bone.
3. kidney.
4.parathyroid glands.
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61. Vit. D & its metabolitesVit. D & its metabolites
1) In the Intestine :
1,25(OH)2D stimulates calcium absorption, by
the duodenum & phosphate absorption by the
jujenum and ileum.
2) On bone :
1,25(OH)2D increases bone resorption by
stimulating osteaclastic differentiation
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62. Vit. D & its metabolitesVit. D & its metabolites
3)In the Kidney3)In the Kidney ::
It inhibits its own synthesis and stimulates its
metabolism.
4)On parathyroid glands4)On parathyroid glands ::
It inhibits the synthesis and secretion of PTH.
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63. Vit. D & its metabolitesVit. D & its metabolites
(C) Clinical Significance :(C) Clinical Significance :
Knowing the concentration of 25(OH)D (which
is the best indication of vit. D nutritional
status )because it is:
1.the main circulatory form
2.varies less from day to day with sun exposure &diet
3.easily measured
is useful in evaluating :
a) hypocalcaemia
b) vit. D status
c) bone disease
d) other disorders of mineral metabolism
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66. CalcitoninCalcitonin
(B) Biological Actions :
Pharmacological doses of calcitonin decrease
serum calcium and ph. concentrations by
inhibiting osteoclastic bone resorption.
Multiple forms of Circulating calcitonin have
been reported in patients with medullary
thyroid carcinomas which occurs as a part of
the syndromes of MEN-2A, MEN-2B and
familial MTC.
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67. MARKERS OF BONE METABOLISM
MARKERS OF BONE FORMATION
1-OSTEOCALCIN
2-ALKALINE PHOSPHATASE
3-PROCOLLAGEN PEPTIDES
MARKERS OF BONE RESORPTION
1-COLLAGEN CROSS LINKS
2-TARTARATE RESISTENT ACID P
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68. MARKERS OF BONE METABOLISM
3-URINARY GALACTOSYL HYDROXYLYSIN
4-URINARY HYDROXYPROLINE
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70. Paget’s disease
Paget’s (pronounced paj-ets) disease affects bones.
Throughout a person’s life bone is constantly breaking
down and growing back. With Paget’s disease the normal
process of bone growth is changed. The bone breaks down
more quickly, and when it grows again it is softer than
normal bone.
Soft bones can bend or break more easily. The area affected
by Paget’s disease can become shorter because the bone
bends.
With Paget’s disease the bone can also grow larger than
before.
Paget’s disease can affect any bone, but usually affects the
skull, the hip and pelvis bones and bones in the legs and
back.
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71. Lab Studies
Biochemical indices reveal elevated alkaline
phosphatase levels of bone origin, due to increased
osteoblastic activity and bone formation.
In limited Paget disease, the alkaline phosphatase
level may be within the reference range.
Procollagen I N-terminal peptide (PINP) recently
has emerged as a sensitive serum marker for bone
formation.
Many patients with elevated alkaline phosphatase
levels have been found to have osteocalcin
measurements within the reference range.
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72.
In Paget disease, urinary hydroxyproline
levels are elevated as they reflect increased
osteoclastic activity and bone resorption.
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