Вы находитесь на странице: 1из 22

Pancreas

Endocrine: Insulin (beta), glucagon (alpha)

Exocrine: Enzyme: Amylase, Lipase, Trypsin, Chymotrypsin, Elastase


Pancreatic Disease:
Acute/Chronic pancreatitis
Carcinoma
Congenital/Structural disease
Directly Measures by Hormonal stimulants: CCK, secretin
Indirectly by Exocrine insufficiency, faecal fat, feacal chymotrypsin, elastase

Acute pancreatitis: Mild/Severe APACHE II (mild >=8)


Complications of AP: Multi-organ failure, necrotizing pancreatitis, pseudocyst,
abscess, obstructive jaundice, bleeding adjacent organ

Diagnosis:
Biochemistry: Plasma amylase (also increased in renal failure, DKA,
macroamylase measure urine amylase as macroamylase cant pass through
glomerulusAmylase-to-Creatinine Ratio ACCR), plasma lipase

Imaging: Ultrasound abdomen, AXR, Contrast enhanced CT, MRI


Plasma amylase (drop faster)
-Rise within 6-12 h, elevate 3-5 days
Plasma lipase
-Rise within 4-8 hours of onset, sustained 8-14 days
Treatment: ERCP
Renal function: Urea, Creatinine (Higher than ref interval Renal failure)
Lipase (not normally detected in urine)
Upon attack of pancreatitis increases within 4-8 hours, peaked at 24hours,
decreases with 8-14 days (longer than amylase)
Measure by Titrimetry, Turbidimetry, Spectrometry, Enzymatic reaction rate

Diabetes (Plasma glucose >5.6)


Type 1: Autoimmune destruction of beta cells ketosis, polyuria, weight loss
Type 2: Genetic, old age, insulin resistance subsequent beta cell failure
Gestational Diabetes (not diabetic before pregnancy) Increased insulin
resistance/fetal hyperinsulinism
Defects in diabetes
Uncontrolled Lipolysis Ketosis
Proteolysis
Hyperglycemia Glycosuria Osmotic diuresis Polyuria, Thirst,
Dehydration, Hypotension
Diabetic microangiopathy
Nephopathy Renal failure
Retinopathy & Cataracts Blindness
Neuropathy Peipheral neuropathy & Autonomic
Atherosclerosis
Lab test for diabetics:
1. HbA1c (>6.5%--> Diabetes)& plasma glucose >11.1mmol/L
2. OGTT
3. Ketones (Beta-hydroxybutyrate[bld], Acetoacetate[urine], Acetone)

4.
NGSP(National Glycohemoglobin Standardization Program) certified assays

Urate and Gout


High UrateCAD & renal disease
Urate (Increase in gout; excrete via kidney/lost in GI)
Major product of catabolism of purine nucleosides (A&G) Xanthine Uric acid
Weak acid
Measurement of Urate( in prechilled 4C herparinzed tubes, analyzed in 4h)
Spectrophotometric/Enzymatic/HPLC
Not visible in X-ray, Calcium visible
Enzymatic colorimetric: Uricase & Peroxidase (red color)
Negative interference: Ascorbic acid, bilirubin, rasburicase
Specimen: herparinzed plasma/EDTA/serum at cool temperature
No refrigeration & acidified precipitation
Add NaOH to urine samples to alkaline it to prevent ppt
Gouty arthritis Identify uric acid crystal in synovial fluid but not quantitatively
Disorders of purine metabolism Hyper or Hypouricemia Test serum uric
acid; urinary uric acid clearance inversely correlated to insulin resistance
Elevate uric acid level
Insulin modify kidneys uric acid handling hyperuricemia
Hyperuricemia-Overproduction
Primary: Inherited enzyme defects Over-production of purine
Secondary: Blood disease, Malignancies, Psoriasis, Drugs/Alcohol
Under-excretion
Renal insufficiency, DKA, Obesity, Endocrine, Drugs

Gout: Monosodium urate crystal deposition


Hyperuricemia*
Three clinical stages
1. Acute gout arthritis (Asymptomatic hyperuricaemia)
Severe pain, redness, swelling, disability;
2. Intercritical/Interval gout
3. Chronic recurrent and tophaceous gout
Characterized biochemically Extracellular fluid urate saturation
Clinical manifestations of 1 or more: Recurrent acute inflame arthritis attack,
chronic arthropathy, accumulation of urate crystal in tophaceous deposits, uric
acid nephrolithiasis, chronic nephopathy
Criteria for clinical diagnosis of gout
-History of one or more episodes of monoarticular arthritis
-Maximum inflame within 24 h
-Unilateral first metatarsophalangeal (MTP) joint attack
-Visible/Palpable lesion Tophus
-Hyperuricemia, obesity, hypertension, hyperlipidemia

Pseudogout=Calcium Pyrophosphate dihydrate (CPPD)


Hypothyroidism
Hypouricemia: Reduced production of purine (liver disease), Increased excretion
Clinical test
Fraction Excretion of Urate (FEua)
24h urine urate
FEua=(UUa x PCr) / (PUa x UCr) x 100% [Normal ~7-10%]
High Hypouricaemia
Ratio between urate clearance & creatinine or insulin clearance
Hereditary Renal Hypouricemia (renal tubular defect in urea reabsorption)
URAT1/SLC22A12 mutation identified Urate anion exchanger Regulate
blood urate levels

Serum uric acid <0.12mmol/L; FEua >10%


Renal handling of uric acid Hypouricemia
Four compartment model
-Glomerular filtration Pre-secretion reabsorption (common defect)
Secretion Post-secretory reabsorption
Net urinary excretion doesnt exceed 10% of filtered load
Exercise induced ARF Hypouricemia(dehydration/uric acid as an
antioxidant)Increase ATP degradation PPT of uric acid
Assess Vitamin Status Analysis of active compound/urinary metabolite with
HPLC, IA but inaccurate
Vit D, PTH help production of calcitriolIncrease Ca and PO4 absorption
Measure by HPLC, MS, IA
B12(Cobalamin), Intrinsic factor, Transcobalamin..--> Anemia
Folate Homocysteine
Affected by genetic/drug effect
Trace elements: Dose-effect (low Deficient; High Toxic)
Iron(serum transferrin bound Fe3+) Deficient/Overload
Ferritin=storage form of Fe; take up Fe2+ Oxidize to Fe3+
(UIBC)Unsaturated Iron binding sites in serum
TIBC=Total Iron binding sites in serum = Fe+ UIBC
Fe saturation=Fe/TIBC *100%
Iron deficient

Primary/Secondary
Fe overload

Serum Fe3+ (transferrin

Low

High

High

Low

bound)
High in morning, low in
afternoon
TIBC (sites)=Fe +UIBC

Unbound Transferrin

High

Low

Ferritin (sensitive marker)

Low

High

Fe saturation (Fe/TIBC*100%)

Low

High (First thing to

Transferrin (mg/dL)
=3.9 * TIBC (umol/L)
Assume all serum Fe bound to
transferrin Overestimated

be abnormal)
Soluble transferrin receptor

High

Low

Cause

APR

Haemochromatosis

Acute phase reaction Increase ferritin, decrease iron & TIBC


Ferritin <113pmol/L usu Fe deficient; >225 Fe replete?
Anemia of chronic disease Increase ferritin, decrease iron & TIBC but anemic
Ferritin also increase in chronic disease
Measure: IA/ TIBC estimation
Test: Haematological markers: Hb/MCV/MCH/HCt/Red cell count
Biochemical markers: Serum Iron(Fe3+ bound to transferrin, not free), Total Iron
Binding Capacity, Serum transferrin, transferrin saturation, ferritin
Soluble transferrin receptor increased in Fe deficiency and increased red cell
turnover
not affected by inflammation
Useful marker to differentiate Anemia of chronic disease from Fe deficiency w/
concurrent inflammation
Soluble transferrin receptor/log ferritin

Gastric
Disorders: Peptic ulcer-Gastric & Duodenal ulcer
By H. pylori; caused/worsen by drugs as aspirin, NSAIDS..etc
Detected by invasive/non-invasive: urea breath test/IgG against H.pylori
Urea breath testing for H. pylori (produce urease that converts urea to NH3)
13C breath test, 14C breath test, Basal gastric output test for gastrin
(Zollinger-Ellison syndrome)
Determine gastric juice by titration with NaOH
Inflammation: Gastritis
Gastroesophageal reflux disease (GERD)
Tumour: gastric cancer

Diarrhoea K/Cl depletion, acid-base abnormalities


Test: Stool culture, examination
Absorption >>> Secretion
Stool weight > 200g/day
Acute <2 wks (infectious agent); Persistent 2-4 wks; (non-infectious)
Acute: Inflammatory diarrhea; disrupt mucosal barrier bloody diarrhea
Non-inflammatory diarrhea enterotoxin excessive ion & water secretion
Poorly absorbed substance net fluid secretion to lumen watery stool

Chronic diarrhea >4 weeks


-Secretory (deranged fluid & electrolyte transport across mucosa, no
malabsorbed solute, persist with fasting)
-Osmotic (poorly absorbable, nonabsorbable CHO, ceases with fasting)
-Steatorrhoea-Pancreatic/Intestinal
(fat malabsorption associated w/ weight loss; osmotic effect of fatty acid)
Foul smelling, gray, sticky
-Dysmotile cause (rapid transit of GI contents, hyperthyroidism
-Inflammatory (Exudation, Fat malabsorption, disrupted fluid/electrolyte
absorption, hypersecretion by inflammatory mediators with pain, fever,

bleeding)
Tests: Hormonal profile, urine laxative screen, radiological studies
Malabsorption: loss of cells for absorption GI tract cant take up dietary
compound
Maldigestion: lacking important digestive enzyme/tissue (genetic/injury)
Symptoms: Failure to thrive, diarrhea, cramping, Flatulence frequent bulky stools,
bloating, abdominal distension
Crohns disease-Inflammatory Bowel Disease
Test: serum, whole blood, urine, feces, breath, sweat, biopsy
Baseline test
GI function; Absorption test should not depend on liver function (bile
salts/pancreatic function: amylase, lipase, proteolytic enzyme)
Never MRI GI motility
Clinical application

Appropriate investigation

Diarrhea

Breath Hydrogen, urine laxative screen, fecal osmotic gap

Pancreatic function

Fecal elastase

Coeliac disease

Anti-gliadin Ab, anti-tissue transglutaminase Ab

CHO

Oral sugar tolerance test mucosal dysfunction, Xylose


absorption test(absorbed rapidly from small intestine,
excrete in urine, test for small intestinal mucosal function
replace by Small intestine mucosal bopsy endoscopy),
Breath Hydrogen

Small intestine bacterial growth

Breath test best eradicate bacteriadisappear


symptoms
Gold standards: Quantitative culture of jejunal aspirate

Fat malabsorption (fecal)

Fecal microscopy, fecal fat, 14C triolein absorption, 14CO2


breath
Qualitative examination of stool (24h not accurate, do 3 or 5
days)

B12

Schilling test

Pernicious anemia

1) Gastric mucosa secrete IF [O/N fast take radioactive

Chronic pancreatitis

cobalamin B12 flush nonradioactive to saturate body

Achlorhydria
Bacterial overgrowth syndrome
Ileal disease

stores collect urine measure radioactivity]


2) Terminal ileum absorb Vit B12 [Taken 3 days after part I,
O/N fast Radioactive B12 + IF flush B12 collect
urine & measure radioactivity]
Part I Normal Part II - Normal

Others

Low

Normal Pernicious Anemia

Low

Low Intestinal malabsorption

Fecal Alpha1-antitrypsin for PLE


Xylose: not normally present in blood, no digestion, absorbed in upper small
intestine, not metabolized by body, filtered by glomerulus
Pancreatic dysfunction, intestinal disease, altered bacterial flora, biliary
obstruction, local disease/surgery, gastric atrophy, disaccharidase deficiency,
protein-losing enteropathy, IEM
Biochemical consequence of Generalized malabsorption
-Steatorrhoea, Fat-sol VIt & Cal Malabsorption, Protein malabsorption, CHO
malabsorption
Biochem: Anemia, Decrease VitB12/Folate/Fe, Ca, PO4, total protein & albumin
Increase plasma ALP, prolong PT, abnormal TFT

Serum protein- part of liver function test


-Total protein
Biuret method-color proportional to protein concentration in sample
Kjeldahl titration
Phenol
Folin-Lowry
Ninhydrin
Cause of hyperproteinaemia: Dehydration, prolonged tourniquet application
-Albumin
-Globulin
Hypergammaglobulinaemia
Polyclonal, monoclonal
Hyperglobulinaemia: serum protein electrophoresis
Urinary bence-jones proteins (BJP): light chain secreted excessively by myeloma
plasma cells

Hypoproteinaemia e.g. pregnancy


Hypoalbuminaemia synthesized usually by hepatic parenchymal cells
-Haemodilution
-Decreased production: malnutrition, liver disease, APR, analbuminaemia
-Altered distribution: infection, inflammation, malignancy
-Loss from body
-Increased catabolism: malignancy, APR
Function of albumin: maintain colloidal osmotic pressure in both vascular and
extravascular spaces, transport protein, buffer
Measures by Bromcresol purple (BCP), BCG, methylorange
Hypogammaglobulinaemia: transient, primary, secondary, protein loss,
pregnancy
Alpha-1 anti-trypsin (AAT) protein inhibitor, Pi ZZ genotype emphysema
-APR, synthesized in liver
Measure by immunonephelometry light scattering

Transferrin-iron transporting protein; transport from absorption site to bone


marrow for erythropoiesis
Measure by TIBC
Soluble transferrin receptor: correlates with erythroid precursors
differentiate iron deficiency anemia from anemia of chronic disease
sTfR/log ferritin
Increased: erythroid proliferation: hemolysis, beta-thal, decreased Fe store
Decreased: chronic renal failure, aplastic anaemia, post bone marrow trannsplant

Ceruloplasmin; age dependent


Synthesized in hepatocytes, secreted into circulation is holoceruloplasmin
Apoceruloplasmin devoid of copper, degraded intracellularly
Disease: Wilson disease
Tested by immunonephelometry
C-reactive Protein (HsCRP) predicts MI, stroke, peripheral arterial disease,
sudden cardiac death; correlates with LDL-cholesterol
Synthesized in liver; induced by IL-6
Stable in circulation, no circardian levels
Predicts CVD risk/MI
Method: immunonephelometry

synthesize

Disease

Measured

CVD/MI

Immunonephelometr

d
C reactive

Liver

Stable level

protein

Ceruloplasmi

Hepatocyte

Wilsons

Immunonephelometr
y

Soluble

Erythroid

Predicts

transferrin

precursors

iron

receptor

deficiency
& anemia
of chronic
disease

Transferrin

Fe transport

TIBC

protein for
erythropoesi
s
Alpha1

Liver

anti-trypsin

Protein

Emphysem

Immunonephelometr

inhibitor

Factors affecting migration of electrophoresis


-Net charge of molecule in solution
-Size & shape of molecule
-electric field strength
-frictional co-efficient
-properties of support medium (non-restrictive/restrictive e.g. PAGE)
-buffer composition (pH determines charge, ionic strength, calactate increase
beta region resolution)
-temperature
-volume of sample
-diffusion
-adsorption
-electroendosmosis
Fixation
-Dry
-PPT protein

-Immunoppt
-Freeze
Detection at 280nm, natural florescence, enzyme coupled reactions,
immunochemical labeled antibody, autoradiography
Stains
Quantitation: elution, densitometry, absorbance at 214nm
Immunofixation: Immunoppt with specific anti-sera after PE
Wash non-ppt protein from gel after incubation
Applications of PE:
-Serum/urine PE as general screen
-Investigation of an elevated globulin fraction
Polyclonal gammopathy, Monoclonal gammopathy, Oligoclonal gammopathy
-Detection of oligoclonal bands in CSF (run Serum & CSF sample tgt)
-Phenotype specific proteins
Multiple myeloma:
single clone of plasma cell proliferation produces monoclonal antibody
Bone pain, height reduction by several inches, weakness & fatigue, weightloss
Bone disease of multiple myeloma; hypercalcemia free light chain assay
Non-secretory myeloma
Light Chain Myeloma
Cryoglobulins: serum protein ppt at temp < body temperature
Positive screening Quantitation of total protein & IgG
Complements
C3 level decreased increase infection risk

Therapeutic drug monitoring


Indications for TDM
Limitation of standard drug dosingi
Serum concentration & clinical response?
Narrow therapeutic index
Long term therapy
Wide interindividual and intraindividual variability in pharmacokinetics
Absence of biomarker w/ therapeutic outcome
Administer w/ other, potentially interacting compounds (drug drug interaction)
Potential patient compliance
Therapeutic group: Anticonvulsants, Cardiovascular(Anti-hypertensives,
anti-arrhythmics), Endocrine
Pharmacodynamics: what drug does to body
Pharmacokinetics: what body does to drug: ADME
Absorption: first pass effect, enterohepatic circulation
Affected by food/co-administered drug
Bioavailability: fractional extent a dose reach site or action
Distribution: affected molecular weight, pKa, lipid solubility
Binding to blood components, receptor, pass membrane, hydrophobicity
Only free drug available for transport across membrane
Affected by abnormal protein status
Weakly bound drug displaced by those w/ high affinity or endogenous FFA
cytotoxicity
Metabolism: convert non-polar to polar water soluble form
Phase 1: functionalization reactions: oxidation, reduction, hydrolysis @ hepatic
cytochrome P450; genetic variation; reaction involve transform prodrug active
Phase 2: Conjugates drug, increase water solubility
Elimination: renal/biliary, intestinal, pulmonary; assessed by creatinine & GFR
Half-life of drug: time required for drug to decline half
Affected by organ failure, intoxicate

Pharmacokinetics
Therapeutic ranges Between MTC and MEC
Peak Level < Minimum Toxic Concentration
Trough > Minimum Effective Concentration [Therapeutic Range]
~5 half lifves steady state
Pharmacogenomics: genetic variation on drug response
Info required for serum drug conc:
Patient ID, time blood taken from last dose (trough vs peak), drug dosage,
Mode of administration, co-med, why take drug, what to monitor, clinical status
Specimen: blood/saliva/urine/sweat/hair
Analysis: IA, Chromatogram HPLC
Special drug group
Anti-convulsants:
Phenyltoin (90% protein bound, easily saturated)
Acute overdose: cerebellar, vestibular effects
Chronic: + behavioral change, increase seizure freq
Assess Toxicity: near peak 4-5 hours after dose
Adequate therapy: trough lv b4 next dose
Phenobarbital: metabolized by liver, 70-100h half life
Side effect: sedation
Valproic acid: absence seizure, highly protein bound
Toxicity: GI, Hyperammonaemia, CNS, teratogenicity
Theophylline: bronchial muscle relaxant; caffeine as metabolite of theophylline
Antibiotics
Aminoglycosides: form complex w/ heparin
Vancomycin: excreted by kidney, auditory nerve toxicity
Cyclosporine: toxic at hepatic, renal, neuro, infective
Area under curve better estimates risk of acute rejection & toxicity
Pre-dose/Trough monitoring

C2: 2 hours post dose


Immunosuppressants
Mood stablizers/antipsychotics
Lithium: treat bipolar illness
Digoxin: Cardiac glycosides, inhibits Na/K ATPase
Toxicity: cardiac failure, cross react digoxin analog endo: uremia, pregnancy; exo:
Chin med, digibind GI, neuro, heart, worsen with hypokalemia,
hypomagnesaemia, hypercalcaemia
Measure at least 6-8h after dose, prefer trough
Methotrexate: antimetabolite, interfere w/ DNA synthesis
Thyroid function
Hypothalamus produces TRH Pituitary produces TSH at Thyroid gland
binds follicle cell receptor thyroglobulin at colloid space
+ Iodine Iodinated tyrosine residues join tgt Triidothyronine (T3) &
Thyroxine (T4) increase T3, T4 in blood Homeostasis negative fdbk to
pituitary, TRH receptor, hypothalamus
Peroxidase oxidize iodine to iodine
If no iodine available, thyroid hormone still maintained
Thyroglobulin
Thyroid hormones
Synthesis of T4 and T3 in thyroid gland
1. Thyroglobulin internalize by endocytosis back in follicle cell
2. Joins with Lysosome Enzyme cleave T3 and T4 from thyroglobulin
3. T3 & T4 released tgt in extracellular space by diffusion
4. Thyroid gland secrete T4:T3 in ratio of 10:1
T3 greater activity than T4; T4 mono-deiodination at outer T3; inner
inactive reverse T3 rT3.
10% T4 & T3 produced daily secrete in bile
Small amounts Urine

Total thyroid hormone (T3,T4) affected by binding proteins (+/-)


Mostly bound to serum protein Thyroxine Binding Globulin TBG (inactive)
-Increased upon pregnancy & estrogen, decrease upon liver disease,
malnutrition, glucocorticoids, nephrotic syndrome, hereditary TBG deficiency
few are free hormones (physiologically active); concentration regulated by
hypothalamus-pituitary-thyroid axis

Thyroid hormones function


Cardiac
-increase heart rate, cardiac contractions, stroke volume, cardiac output
Muscle
-rate & force of skeletal muscle contraction
Stimualtes BMR
-Increase activity of adrenal medulla (sympathetic, glucose production)
-Increase intestinal glucose reabsorption
-Increase mitochondrial oxidative phosphorylation (energy)
-Increase heat production
Investigation
Total thyroid hormone assay-estimation of TBG
T-uptake and Free thyroxine index (FTI): resin uptake method; resin used to
separate unbound labeled thyroid hormone(resin bound) from bound to TBG
Amount of resin bound hormone inversely proportional to unsaturated
binding sites of TBG
FTI only correlates well w/ free T4 only patient w/ mild TBG abnormalities
FT4,FT3: ref method for free thyroid hormones for equilibrium dialysis
Estimated by Immunoassays, unit in pmol/L
TSH inversely proportional to plasma T3,T4 level
Initial treatment of Hyperthyroidism look at FT4
Thyroid antibodies: Graves disease
TSH receptor autoantibodies: like TSH that binds to TSH receptor

overproduction of thyroid hormones=Hyperthyroidism; detection/exclusion of


Graves disease
Anti-thyroid peroxidase antibody, Anti-thyroglobulin antibody
-Confirmation/exclusion of autoimmune thyroiditis
TRH stimunlation test: determine TSH at 0,30,60,120 minutes
Hyperthyroidism Response is flat
Differentiate secondary and tertiary hypothyroidism
Pituitary hypothyroidism Flat response
Hypothalamic hypothyroidismDelayed positive response
Red cell zinc: low in hyperthyroidism
Tumor markers: Thyroglobulin: correlates w/ size of thyroid gland
Increased in inflammation of thyroid gland; increased in most differentiated
thyroid cancers
Calcitonin: produced by C cells of thyroid gland; diagnosis & monitor marker of
medullary thyroid cancer
TSH assay-third generation: differentiate mildly subnormal TSH from highly
suppressed TSH levels; identify sick euthyroid syndrome
Free T4
Solid phase competitive enzyme immunoassay
-Highly specific T4 polyclonal antibody bound to polystyrene well
Test Sample + T4 enzyme conjugate add to each antibody coated well
Incubate 60 mins T4 in patient sera competes with T4 enzyme-conjugate for
binding sites on coated wells
Amount of T4 in patient sample inversely proportional to amount of T4
enzyme conjugate to well
Free T3
-2 steps IA detect free T3 in sample using Chemiluminescent Microparticle
Immunoassay
Sample + Anti-T3 coated paramagnetic microparticles combined
Free T3 in sample binds to anti-T3 coated microparticles
T3 acridinium labeled conjugate added
Reverse relationship between free T3 in sample & Relative Lights Unit

TSH assay: 2 step IA: determine presence of thyroid stimulating hormone in


human serum & plasma using Chemiluminescent Microparticle Immunoassay
Technology
1. Anti-beta TSH antibody coated paramagnetic microparticles + TSH assay
diluent
2. TSH in sample binds anti-TSH antibody coated microparticles
3. After washing, anti-alpha TSH acridinium labeled conjugate
4. Pretrigger & Trigger solution add to reaction mixture measure RLU
5. Direct relationship b/w TSH in sample & RLU
Hyperthyroidism:excess thyroid hormone levels
Symptoms: nervousness, goiter
Cause: most commonly Graves disease (Female >>Male)
Lab results: Suppressed TSH, Raised FT3, FT4.
T3 toxicosis: normal FT4, raised FT3.
Subclinical hyperthyroidism: suppressed TSH w/ normal thyroid hormones
Transient hyperthyroidism in pregnant women w/ severe vomiting: Thyroid
hormone normalizes in 2 and 3 trimester
hCG-Mild Thyroid stimulating activity
Peripheral resistance to thyroid hormones: patient is euthyroid
Increase FT4 to a lesser degree FT3
TSH normal/slightly increased/not completely suppressed
Absence of usual symptoms & metabolic consequences of increase in thyroid
hormone
Hypothyroidism: decrease level of thyroid hormones: slow speech, cold
Deficiency of thyroid hormone during development short stature, mental
deficits
Adult onset (myxedema) Severe hypothyroidism
Lab results: decreased FT4, FT3, increased TSH; (FT4 better analysis than FT3)
Cause: Hashimoto thyroiditis (Female >>> Male); present w/ goiter
Iodine deficiency also goitrous
Subclinical hypothyroidism: low normal serum thyroid hormones, mildly
raised TSH

Sick euthyoid syndrome: abnormalities in thyroid function in patient w/ serious


illness not caused by primary thyroid/pituitary dysfunction
Low T3 level w/ increased rT3 & low normal TSH, T4 levels
Iron
-O2 transport
-energy metabolism
-Hb 67%
-storage iron 27%, myoglobin 3.5%, tissue iron 0.2%, transport iron 0.08%
Iron deficiency: intake less, loss more (bleed)
Iron overload:
Hemosiderosis (no tissue injury),
Hemachromatosis (tissue injury)
-Bronzing of skin
-Cirrhosis
-Diabetes
-Endocrinopathies
-Cardiomyopathies
-Arrhythmias
-Arthopathies
Detection: Chromogenic
Measure after release from transferrin (Fe3+ only)
Ferritin: protein shell surrounding iron core
=Fe store in body
Transferrin
Measure as Unsaturated Iron Binding Capacity
Saturate Fe3+ binding of transferrin Remove Fe3+ Check saturation %
Lab assessment: Historical, Hematological, Biochemical
Biochemical: Serum ferritin, iron concentration, TIBC, Transferrin %

Stage

Plasma Fe

TIBC

Transfer

Ferritin

Plasma

Negative

rin

(sensitive and specific

soluble

APR

saturatio marker for Fe deficiency in

transferrin

metabolically stable patient)

receptor

50%

(Fe/TIB

Positive APR

lower in

C)

pm

Negative

Reflects
Cut off <34pmol/L

APR

cellular Fe
status

>225pmol not deficiency

<upregulate>

Tells
how

Not affected

much Fe

by chronic

actually

disease/APR

bound
I: Depletion of Fe stores

Normal

Normal Normal

Low

Normal

II: Functional Fe deficiency

Low

High

Low

High when

Low

increased
effective or
ineffective
erythropoiesi
s
III: Fe deficiency anemia

Low

High

Low

Low

High

Low

Low or

Low or

<255pmol/L

High

normal

normal

With low Hb
Iron deficiency + anemia of
chronic disease
Anemia of chronic disease

Low

Low

Low

High

Normal

Fe overload

High

Low or

High

High

-Normal

normal
Acute Phase reaction

Low

Low

Low

High

ID+ APR

Low

Low

Low

<225pmol/L

Transferrin saturation% can be due to afternoon samples, ACR, OC pills


Clinical decision cutoffs
-Age specific and method dependent

Porphyria: Enzyme related disease: IEM


PBG: Porphobillinogen
Acute Prophyria
-suspected acute attack
Measure: Urine PBG (10X high), fecal porphyrin, fractionated fecal porphyrins,
plasma fluorescence emission spectroscopy
ALA dehydratase deficiency porphyria
Acute Intermittent Porphyria (PBG elevate for weeks or even months after
attack): when normal total fecal porphyrin
Congenital Erythropoietic Porphyria
Porphyria Cutanea Tards
Hereditary Coproporphyria (PBG returns to normal once resolve)
Abnormal total fecal porphyrin
Increased coproporphyrin III upon Fractionated fecal porphyrins
Variegate Porphyria (PBG returns to normal once resolve)
High PBG
Abnormal total fecal porphyrin
Characteristic peak at 624-628nm
Increased portoporphyrin IX
Erythropoietic Protoporphyria