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Clinical Chemistry Review Booklet (Part 2)
Clinical Chemistry Review Booklet (Part 2)
The first digit represents the class of enzymes. The second and third digits represent
subclass of enzymes. The final number represents the serial number specific to each
enzyme.
V = Vmax [S]
Km + [S]
Where V stands for velocity, Vmax for maximum velocity, S for substrate and
Km stands for Michaelis-Menten constant of enzyme for specific substrate
2. pH
Optimum range for most enzymes is at 7.0 – 8.0
Sudden changes may cause denaturation or alter the charge of amino acid residue on the
active site; however, it can be prevented by means of buffer solutions
3. Temperature
Enzyme are active at 5C, 30C, or 37C
37C is the optimum temperature for enzymatic activity
The rate of denaturation is significant at 40 – 50C
60 – 65C may cause inactivation of enzymes
Temperature coefficient (Q10) – for every 10C increase in temperature, enzyme reaction
doubles
In lab determinations, temp should not deviate from + 0.1C from the required temp to
maintain accuracy of results
o Creatine kinase – 37C
o Amylase – 40C
4. Storage
Repeated freezing and thawing denatures enzymes
-20C – preservation for longer period of time
2 – 8C – ideal storage temp for substrate and coenzymes
RT – ideal storage for LDH4 and LDH5; should not be stored less than 0C without loss
of enzyme activity
5. Cofactors – nonprotein substances that may be necessary for enzyme reaction to take place
Inorganic cofactors/activators – calcium, magnesium, manganese and chloride
Organic cofactors/coenzymes
a. NAD and flavine – required by oxidoreductases and dehydrogenases
b. Pyridoxal phosphate – required by transaminases
Metalloenzymes – inorganic ion attached to a molecule (catalase and cobalt)
Hydrolases require no cofactors
6. Inhibitors
a. Competitive inhibition
With a substrate concentration higher than the inhibitor concentration, the inhibition
is reversible
Physically binds to the active site of an enzyme
b. Non-competitive inhibition
Binds an enzyme at a place other than the active site
Increasing substrate concentration does not reverse the inhibition
c. Uncompetitive inhibition
Inhibitor binds to enzyme-substrate complex
Increasing the substrate concentration results in more ES complices thereby
increasing inhibition
7. Hemolysis – falsely elevates most enzyme
8. Lactescence – falsely decreases enzyme concentration
Methods:
1. Electrophoresis – L (most anodal) BPI
2. Heat Stability
56C for 10 minutes P (same as carcinoplacental isoenzymes) ILB
65C for 30 minutes (Placental ALP resists denaturation at this temp)
3. Chemical Inhibition
All are inhibited by phenylalanine
Liver and bone – inhibited by Levamisole reagent
Bone – inhibited by 3M urea
4. Requires a pH of 9 - 10
Carcinoplacental Isoenzymes
1. Regan – found in lung, breast and gynecological cancers
2. Nagao – found in adenocarcinoma of pancreas, and bile duct, and pleural cancer,
inhibited by leucine
**Same structure and heat stability with PLACENTAL isoenzyme but same mobility
with BONE isoenzyme
ACID PHOSPHATASE
Methods:
1. Requires a pH of 5.0
2. Inhibited by fluoride, oxalate, heparin and prolonged storage at RT and tartrate
ASPARTATE AMINOTRANSFERASE
Clinical Significance:
PRONOUNCED MODERATE ELEVATION SLIGHT ELEVATION
ELEVATION
(5x or more X ULN) (3-5X ULN) Up to 3X ULN
Acute hepatocellular damage Biliary tract obstruction Pericarditis
Viral hepatitis Cardiac arrhythmias Cirrhosis
100XULN Congestive heart failure Pulmonary infarction
Cirrhosis 4XULN Metastatic tumor in liver Delirium tremens
Myocardial infarction Muscular dystrophy Cardiovascular accident
Circulatory collapse (shock)
Acute pancreatitis
IM
Isoenzyme of AST:
1. Cytoplasmic / Extramitochondrial AST
More predominant in plasma or serum
Half-life 17 hours
2. Mitochondrial AST
Cause of tissue necrosis
Half-life 87 hours
Method:
1. Karmen Method
pH 7.5
Uses malate dehydrogenase
ALANINE AMINOTRANSFERASE
Most liver specific and more sensitive screening test for post-transfusion hepatitis or
occupational toxic exposure
Clinical Significance:
1. In acute hepatocellular injury, in < 24 hours
AST > ALT
In 24 – 48 hours following onset of injury
ALT > AST – except in alcohol-induced liver damage / cirrhosis
De Ritis Ratio: ALT/AST 3 – 4: 1
AST/SGOT ALT/SGPT
Major organ affected Heart Liver
Substrate Aspartic alphaketoglutaric Alanine alphaketoglutaric acid
acid
End-product Glutamic acid + Oxaloacetic Glutamic acid + Pyruvic acid
acid
Color developer 2,4 – DNPH
Color intensifier 0.4 N Sodium hydroxide
Method REITMAN AND FRANKEL
Tissue source: Major – Acinar cells (glandular cells) of pancreas and salivary glands
Minor – fallopian tube, small intestine
Clinical Significance:
1. Acute pancreatitis (earliest) 2.5 X ULN
Elevates at 2 – 12 hours; peaks at 24 hours and normalizes in 3 – 5 days
2. Salivary gland disorders(mumps, parotitis) intestinal disorders, ruptured ectopic
pregnancy
Isoenzymes:
1. P (amylopsin)
Secreted by pancreas; major isoenzyme present in the urine
Slower in electrophoresis
2. S (ptyalin)
Secreted by salivary glands; 2/3 of AMS activity in normal serum
P3 is most specific to acute pancreatitis
Macroamylasemia – amylase becomes large when complexed with Ig; increased
amylase level due to ↓ renal clearance
LIPASE
Methods:
1. Titrimetric – hydrolyzed into monoglyceride, diglycerdie and FFA
2. Turbidimetric – triglyceride form emulsions that scatter light
3. Colorimetric:
Cherry-Crandal (reference method)
Hydrolysis of olive oil after incubation for 24 hours at 37C and titration of fatty acids
using sodium hydroxide
Substrate: 50% olive oil (now – triolein)
4. Tietz and Fiereck
5. Peroxidase coupling – most commonly used method, does not use olive oil
LACTATE DEHYDROGENASE
Notes:
1. Highest elevation is seen in PERNICIOUS ANEMIA
2. LDH-2 is the major isoenzyme in normal serum
Normal: LDH2 > LDH1
Flipped pattern: LDH1 > LDH2 – seen in AMI and hemolytic disorders
** In AMI, LDH levels begin to rise within 12-24 hour, reach peak levels within 48-72
hours, and may remain elevated for 10 days
3. H has greater affinity for lactate (forward)
4. M has greater affinity for pyruvate (reverse)
5. LDH-6 – alcohol dehydrogenase (arteriosclerotic cardiovascular failure)
Methods:
1. Forward reaction (WACKER) – reaction at pH 8.8
3. Wrobleuski Cabaud
4. Berger-Broida
5. Alpha-hydroxybutyrate dehydrogenase represents LD-1 activity
CREATINE KINASE
Major tissue source: Brain, smooth and skeletal muscles,and cardiac muscles
Isoenzyme Tissue Condition
CK-MM Heart, skeletal muscles Myocardial infarction
Malignant hyperthermia
Muscular dystrophy
Physical activity
Polymyositis
Hypothyroidism
Skeletal muscle disorder
Intramuscular injection
CK-MB Heart, skeletal muscles Myocardial infarction
Malignant hyperthermia
Ischemia
Angina
Reye’s syndrome
Rocky Mountain SF
Polymyositis
Muscular dystrophy-
Duchenne
Inflammatory heart disease
Cardiac surgery
Carbon monoxide poisoning
CK-BB Colon, stomach, brain, Seizure
bladder, lung, uterus, prostate, Placenta or uterine trauma
thyroid Anoxic encephalopathy
Reye’s syndrome
Malignant hyperthermia
Acute or chronic renal failure
Cerebrovascular accident
CNS shock
Carcinoma
Carbon monoxide poisoning
PRONOUNCED ELEVATION MILD OR MODERATE ELEVATION
5 or ↑ X ULN 2 – 4 X ULN
Duchenne’s muscular dystrophy Severe execise, trauma, surgical procedure,
Polymyositis intramuscular injection
Dermatomyositis Delirium tremens, alcoholic myopathy
Myocardial infarction Myocardial infarction, severe ischemic injury
Pulmonary infarction
Pulmonary edema
Hypothyroidism
Acute agitated psychoses
Isoenzymes:
1. CK-1 – most anodal and labile isoenzyme (CK-BB)
2. CK-3 – least anodal and major isoenzyme (CK-MM)
Highest elevation is seen in DMD (total CK)
3. Macro-CK – CK-BB complexed with IgG/IgA; migrates midway between CK-MM and
CK-MB
4. CK-Mi – associated with external surface of inner mitochondrial membrane of the brain,
muscle, liver cells; cathodal to CK-MM
Methods:
1. Forward reaction: TANZER-GILBARG pH = 9.0
Creatine is converted to creatine phosphate
2. Reverse reaction: OLIVER-ROSALKI pH = 6.8
Creatine is produced from creatine phosphate
Note:
1. Light and pH sensitive; lost with excessive storage
2. N-acetylcysteine is added to CK reagent to activate the enzyme and partially reversed the
inhibition of oxidized sulfhydryl groups
3. Following myocardial infarction, the CK-MB levels begin to rise within 4 to 8 hours,
peak at 12 to 24 hours, and return to normal levels within 48 to 72 hours.
ALDOLASE
GAMMAGLUTAMYL TRANSFERASE
5’ NUCLEOTIDASE
PSEUDOCHOLINESTERASE
GLUCOSE-6-PHOSPHATE DEHYDROGENASE
Tissue source: Adrenal cortex, spleen, RBC, lungs, thymus, lactating mammary glands
Significance: ↑ Hepatic disorder and AMI
Deficiency may lead to drug-induced hemolytic anemia (quinine and sulfonamides)
Favism
ELECTROLYTES
Volume and Osmotic regulation (Na+, K+, Cl-)
Maintainance of acid-base balance (HCO3-, K+,Cl-)
Myocardial rhythm and neuromuscular excitability (K+, Mg++, Ca++)
Cofactors in enzyme activation (Mg++, Ca++, Zn++)
Production and use of ATP from glucose (Mg++, PO4-3)
Regulation of ATPase ion pumps (Na+, K+, Ca++, Mg++)
Blood coagulation (Ca++, Mg++)
Sodium
90% of total plasma volume
Major extracellular cation and major determinant of plasma osmolality
Glass membrane is used for ISE determination
Reference range: 135 – 145 mmol/L
< 125 – neuromuscular injury
< 120 – need immediate attention
Regulation:
1. Intake of water in response to thirst
2. Blood volume states
3. Excretion of water
Hypernatremia Hyponatremia
1. Excess water loss 1. Increased sodium loss
Diabetes insipidus Diuretic use
Renal tubular disorder Saline infusion
Prolonged diarrhea 2. Increased water retention
Profused sweating Renal failure (RTA)
Severe burns Nephrotic syndrome
Vomiting Aldosterone deficiency
Fever Cancer
Hyperventilation Syndrome of inappropriate ADH
2. Decreased water intake secretion
3. Increased intake or retention Hepatic cirrhosis
Hyperaldosteronism (Conn’s disease) Primary polydipsia
Sodium bicarbonate infusion CNS abnormalities – meningitis,
Increased oral or IV intake of NaCl encephalitis, MS
Ingestion of sea water Myxedema
Categories of Hypernatremia
1. Hypernatremia with < 300 mOsm/kg
Diabetes insipidus
2. Hypernatremia with 300 – 700 mOsm/kg
Osmotic diuresis of patients with DM and partial ADH defect
3. Hypernatremia with > 700 mOsm/kg
Insensible loss of water, GI loss of hypotonic fluid
Potassium
Major intracellular cation
Regulation of volume and osmolality, myocardial contraction and neuromuscular excitability
along with calcium and magnesium
Valinomycin membrane is used for ISE determination
Reference range: 3.5 – 5.1 mmol/L
< 3 mmol/L – muscle weakness and paralysis; kalium administration
> 10 mmol/L – cardiac arrest
8 mmol/L – neuromuscular injury
Regulation:
1. Na-K ATPase pump – loss occurs when inhibited by hypoxia, hypomagnesemia, and
digoxin toxicity
2. Beta-blockers – (propranolol) group of antihypertensives which impairs cellular entry of
potassium
3. Insulin – promotes entry of K into skeletal muscle and liver
4. Catecholamines – promotes cellular entry of K
5. Exercise
Hyperkalemia Hypokalemia
1. Decreased renal excretion 1. Gastrointestinal loss
Acute or chronic renal failure Gastric suction and laxative abuse
Severe dehydration Intestinal tumor and malabsorption
Addison’s disease Cancer and radiotherapy
2. Extracellulat shift Vomiting and diarrhea
Acidosis 2. Renal loss
Muscle/cellular injury Diuretics use (thiazides)
Vigorous exercise Hyperaldosteronism
Digitalis intoxication Cushing’s syndrome
3. Increased intake – oral or IV Leukemia
infusion Bartter’s syndrome
4. Use of immunosuppressive drugs Gitelman’s syndrome
Tacrolimus and cyclosporine Liddle syndrome
Malignant hypertension
3. Intracellular shift – alkalosis and
insulin overdose
Pseudohyperkalemia – associated with sample hemolysis, thrombocytosis, prolonged
tourniquet application, fist clenching, blood stored in ice, IV fluid and high blast counts in acute
or accelerated phase leukemias
Chloride
Major extracellular anion
Involved in the maintainance of osmolality, blood volume and electric neutrality
It is the chief counterion of sodium in the ECF. It promotes maintenance of water balance in
conjunction with sodium and the only anion to serve as an enzyme activator.
Reference range: 98 – 107 mmol/L
Hyperchloremia Hypochloremia
Renal tubular acidosis – alkaline urine due to Prolonged vomiting
wasting of bicarbonate ions Aldosterone deficiency
Diabetes insipidus Metabolic alkalosis
Salicylate intoxication Salt-losing nephritis
Primary hyperparathyroidism
Metabolic acidosis
Prolonged diarrhea
Chloride maintains electric neutrality in 2 ways: (1) Sodium is reabsorbed with chloride
in the PCT. (2) Carbon dioxide from cellular metabolism enters the cell to form carbonic
acid by the action of carbonic anhydrase. Carbonic acid splits into hydrogen ions and
bicarbonate which diffuses into the plasma and chloride enters the cell (chloride shift)
Chloride is inversely related to bicarbonate ions
Magnesium
2nd most abundant intracellular cation
Reference range: 0.63 – 1.0 mmol/L
Distribution:
1. Bones – 53%
2. Muscles and tissues – 46%
3. Plasma – 1%
a. 61% - free; ionized (most active)
b. 34% - protein-bound
c. 5% - bound to ions including phosphate and citrate
Regulation:
1. Diet
2. Intestinal absorption – PTH increases absorption
3. Renal reabsorption – PTH increases absorption
4. Renal excretion affected by hormones – aldosterone and thyroxine promotes renal
excretion
Calcium
Distribution:
1. 99% - skeleton
2. 1% - ECF, plasma
a. 50% - ionized
b. 40% - bound to proteins
c. 10% - bound to ions
Regulation:
Parathyroid hormone Enhance resorption from bone
Stimulate Vitamin D synthesis
Enhance renal tubular reabsorption
Calcitonin Stimulate calcium uptake by bone
Decrease renal tubular reabsorption (promotes
renal excretion of calcium)
Vitamin D metabolites Enhance intestinal absorption
Enhance resorption from bone
Increase renal tubular reabsorption
Hypercalcemia Hypocalcemia
Cancer Calcitonin
Hyperthyroidism Hypoparathyroidism
Iatrogenic disease Alkalosis
Multiple myeloma Renal failure
Hyperparathyroidism Vitamin D deficit
Sarcoidosis
Phosphate
Omnipresent in living cells; predominant intracellular anion
It is inversely related to calcium. It is essential for the insulin mediated entry of glucose into
cells by a process involving phosphorylation
Common phosphate esters: DNA, RNA, ATP, creatine phosphate, phosphoenolpyruvate
Regulation:
1. PTH – promotes renal excretion of phosphate
2. Vitamin D – promotes intestinal absorption and renal reabsorption of phosphate
3. Calcitonin – inhibits bone resorption
4. Growth hormone – decrease renal excretion of phosphate
Hyperphosphatemia Hypophosphatemia
Hypoparathyroidism Alcohol-abuse – most common cause
Renal failure (tubular failure) Primary hyperparathyroidism
Lymphoblastic leukemia Avitaminosis D
Hypervitaminosis D Myxedema
Bicarbonate
Second most abundant extracellular anion
Represents more than 90% of plasma carbon dioxide
Plays a role in the maintenance of acid-base balance
Clinical significance:
a. ↑ - metabolic alkalosis
b. ↓ - metabolic acidosis
Lactate
By-product of anaerobic glycolysis
Removed from the blood by the liver (gluconeogenesis)
Clinical significance:
a. ↑ lactate – sensitive indicator of tissue hypoxia
1. Type A lactic acidosis (hypoxic)
Hypovolemic or hemorrhagic shock, congestive heart failure, pulmonary edema,
severe blood loss
2. Type B lactic acidosis (metabolic)
Leukemia, diabetes mellitus, severe infections, liver and renal disease, alcohol or
salicylate poisoning
** Normal: 1 mol of glucose (aerobic) pyruvate – acetyl CoA citric acid cycle produces 38
moles of ATP
** Under hypoxic conditions, acetyl CoA does not occur, so NADH accumulates. Conversion of
pyruvate to lactate under anaerobic metabolism (2 moles of ATP)
ANION GAP
Difference between unmeasured cation (Na+ and/or K+) and unmeasured anions (Cl and HCO3)
Reflects the concentration of unmeasured ions
There is a gap because the unmeasured cations and anions are not considered
AG = Na – (Cl + HCO3)
Reference range: 7 – 16 mmol/L
Primary – genetic,
autosomal recessive
Secondary – acquired,
iron overload (increased
dietary intake,
transfusion); metabolic
dysfunction – liver
disease and porphyria
cutanea tarda
HENDERSON-HASSELBACH EQUATION:
Represents acid-base balance relationship: 20:1 ratio of bicarbonate-carbonic acid buffer.
where:
pKa = is 6.1; combine hydration and dissociation constants for carbon dioxide in blood
conjugate base = bicarbonate
weak acid = carbonic acid
1. pH
Normal pH: 7.35 – 7.45
< 7.35 – acidosis
> 7.45 – alkalosis
2. pCO2
Normal: 35 – 45 mmHg
< 35 mmHg – Respiratory alkalosis
> 45 mmHg – Repiratory acidosis
3. HCO3
Normal: 21 – 28 mEq/L
< 21 mEq/L – Metabolic acidosis
> 28 mEq/L – Metabolic alkalosis
4. Degree of Hypoxemia
Normal: pO2 – 80 – 100 mmHg
61 – 80 mmHg – MILD
41 – 60 mmHg – MODERATE
40 mmHg or less – SEVERE
NOTES:
1. For every degree of fever in the patient, pO2 will fall 7% and pCO2 will rise 3%
TUMOR MARKERS
ENDOCRINOLOGY
Denotes secretion of biologically active substances
Controls flow of information between cells and tissues
Releases hormones into the circulation to convey information to target cells that contain
cognate hormone receptors
ROLES OF HORMONES:
1. PARACRINE – when hormones act on neighboring cells
2. JUXTACRINE – when hormones remain bound in the membrane of 1 cell and react with a
receptor on a juxtaposed cell
3. AUTOCRINE – when hormones are released and act on receptors located on the same cell
4. INTRACRINE – when hormones act inside the cell without being released
Structure Hormones
Peptide Insulin, PTH, LH, FSH, TSH, TRH, ACTH, prolactin, GH,
calcitonin, glucagon
Steroid Cortisol, progesterone, estrone, estradiol, testosterone, aldosterone
Amino acids Epinephrine, norepinephrine, T4 and T3
Fatty acids Prostaglandins
A. HYPERSECRETION
GIGANTISM
GH-producing tumor before epiphyseal closure (childhood)
ACROMEGALY
GH-producing tumor after epiphyseal closure (adulthood) ; bony and soft tissue
overgrowth
LAB DIAGNOSIS:
Screening test: Somatomedic C or Insulin-like Growth Factor I
Confirmatory test: OGTT (75g oral glucose load)
B. HYPOSECRETION
PITUITARY DWARFISM
may be due to tumors or inevitable consequence of aging
LAB DIAGNOSIS:
Screening test: Somatomedin C or Insulin-like Growth Factor I
Confirmatory test: (1) Insulin Tolerance test (gold standard) (2) Arginine Stimulation
test (2nd confirmatory test)
SHEEHAN’S SYNDROME
monotropic hormone deficiency following post-partum ischemic necrosis of the pituitary
following a complicated delivery
KALLMANN’S SYNDROME
panhypopituitarism; complete loss of pituitary function
PROLACTIN
Stress hormone
Has a diffuse target tissue and lacks a single endocrine end organ
Role in reproduction (lactation)
TRH and estrogen – directly stimulates prolactin production by lactotropes
Primary regulation – tonic inhibition by dopamine
HYPERPROLACTINEMIA
PROLACTINOMA – most common pituitary tumor
Manifestations include menstrual irregularity, amenorrhea, infertility, reduced libido and
erectile dysfuntion
OXYTOCIN
Critical role in lactation
Major role in labor (contraction of gravid uterus) and parturition
VASOPRESSIN / ADH
Major role in renal free water excretion – reabsorption of water in renal tubules
Potent pressor agent – effects blood clotting by promoting factor VII release from
hepatocytes and vWf release from the epithelium
A. HYPOSECRETION
DIABETES INSIPIDUS
Characterized by copious production of urine (polyuria) and intense thirst (polydipsia)
HYPOTHALAMIC DI NEHPROGENIC DI
Decreased ADH production With normal ADH production
No problem with kidney cells Unresponsive kidney cells to ADH produced
by hypothalamus
3. THYROID GLAND
2 types of cells: (1) thyroid follicular cells - produce T3 and T4 (2) thyroid parafollicular
cells / C-cells – produces calcitonin
Iodine can be found in dietary iodide such as seafood, salt and dairy products
Thyroxine (T4) – represents 80% of thyroid hormones; serves as pro-hormone for T3
Triiodothyronine (T3) – represents 20% of thyroid hormones; produced by conversion of
T4 within the liver and periphery; encourages cell differentiation, tissue growth and
development and calorie metabolism
Calcitonin – participates in calcium homeostasis by responding to hypercalcemia; inhibits
bone-dissolving activity of osteoclasts
A. HYPERSECRETION
THYROTOXICOSIS
Caused by excessive thyroid hormone in the circulation
Due to pituitary tumors, excessive TSH secretion, thyroid carcinoma, and toxic
multinodular goiter
↑ T3 and T4; ↓ TSH and TRH
GRAVE’S DISEASE
Autoimmune disorder in which immunoglobulins are produced that activate the TSH
receptor
B. HYPOSECRETION
Serum level of thyroid hormone is insufficient to provide for the metabolic needs of
the cell
Results in CRETINISM in children and MYXEDEMA in adults
PRIMARY HYPOTHYROIDISM
Inadequate secretion of thyroid hormones
↓ T3 and T4
SECONDARY HYPOTHYROIDISM
Decrease in production of TSH leading to low serum levels of thyroid hormones
↓ TSH ; ↓ T3 and T4 ; compensatory mechanism: ↑ TRH
TERTIARY HYPOTHYROIDISM
Hypothalamic failure leading to a lack of TRH production
↓ TRH ; ↓ TSH ↓ T3 and T4
CHRONIC IMMUNE THYROIDITIS (HASHIMOTO’S THYROIDITIS)
Caused by a genetic abnormality in the immune system
Involves massive infiltration of the thyroid gland by lymphocytes
Same symptoms with hypothyroidism
C. LABORATORY DIAGNOSIS
1. T3 Resin Uptake
Analyzes the capacity of thyroid binding globulin to bind thyroid hormones
Indirect measurement of free binding sites on the TBG molecule
4. PARATHYROID GLAND
Parathyroid hormone – involved in the metabolism of both calcium and phosphorus by
the kidneys and bones
In bone – increases bone resorption of calcium into serum
In kidneys – increases renal reabsorption of calcium
PTH, via 1, 25 (OH)2D, promotes intestinal absorption of calcium
A. HYPERSECRETION
Leads to extreme bone wasting and fractures
PRIMARY HYPERPARATHYROIDISM
Parathyroid adenoma
↑ Calcium ; N to ↓ Phosphorus
SECONDARY HYPERPARATHYROIDISM
Conditions associated with the attempt to compensate for hypocalcemic states
↓ Calcium ; ↑ Phosphorus
B. HYPOSECRETION
Reults in tetany (involuntary contraction of the muscles of the hand, feet, legs and back
and may cause spasm of the muscles of the wrist and hand (Trousseau’s sign)
5. ADRENAL GLAND
A. ADRENAL CORTEX
Derived from urogenital ridge ; yellow on autopsy
ALDOSTERONE
Regulated by RAAS which is activated by:
o ↓ Plasma osmolality
o ↓ Sodium concentration in the blood
o ↓ Circulating blood volume
o ↓ Blood pressure
Reabsorption on sodium
Excretion of potassium
Excretion of hydrogen ions
A. HYPERSECRETION
CONN’S DISEASE
Adrenal tumor synthesizing aldosterone autonomously
PRIMARY HYPERALDOSTERONISM
Localized on the gland (tumors)
SECONDARY HYPERALDOSTERONISM
Hypersecretion of renin
LABORATORY DIAGNOSIS
B. HYPOSECRETION
PSEUDOALDOSTERONISM
Bartter’s syndrome – bumetanide-sensitive chloride channel mutation
Gitelman’s sundrome – thiazide-sensitive transporter mutation
CORTISOL
Critical to hemodynamic and glucose homeostasis
Maintain blood glucose by inducing lipolysis and amino acid release from muscle
breakdown for conversion into glucose (gluconeogenesis) and storage as liver glycogen
Cortisol levels are highest in the morning (8:00 am) and lowest at night (10:00pm – 12:00
am)
A. HYPERSECRETION
LABORATORY DIAGNOSIS
1. Screening test:
24-hr urine free cortisol test – most sensitive and specific; method: HPLC
Overnight dexamethasone suppression tests – most widely used (1mg)
Salivary cortisol test
2. Confirmatory test:
Low-dose dexamethasone suppression test (0.5 mg)
Midnight plasma cortisol
CRH Stimulation test
B. HYPOSECRETION
LABORATORY DIAGNOSIS
2. Metyrapone Test
Inhibitor of 11B-hydroxylase
Measures the ability of the pituitary gland to respond to declining levels of
circulating cortisol
Confirmatory for 2o or 3o adrenal insufficiency
ANDROGENS
Necessary for development of secondary sex characteristics in males and females
Virilization in men may lead to infertility with feminizing effects due to low testicular
testosterone production, deceased hair growth and loss of muscle mass
Virilization in women may lead to infertility with masculinizing effects (hirsutism,
menstrual irregularities and male pattern baldness)
B. ADRENAL MEDULLA
Derived from the neural crest ; mahogany on autopsy
CATECHOLAMINES
Norepinephrine and epinephrine (9:1)
Promotes fight-or-flight response
Increases cardiac output and blood pressure
Metabolites: (1) metanephrines (2) vanillylmandelic acid
DOPAMINE -Catecholamine produced in the body by he decarboxylation of 3,4-
dihydrxyphenylalanine (DOPA)
o Major intact catecholamine in urine
o Major metabolite: Homovanillic acid (HVA)
o Found in high concentrations in urine in children with neuroblastoma
A. HYPERSECRETION
PHEOCHROMOCYTOMA
Catecholamine-producing tumor arising from chromaffin tissue
LABORATORY DIAGNOSIS
1. HPLC/RIA
Most specific and sensitive screening test for plasma metanephrines
6. GONADS
A. TESTES
Predominant hormone: testosterone
Controlled by pituitary hormones:
o Follicle-Stimulating hormone (FSH) – acts primarily on germinal stem cells
o Luteinizing hormone (LH) – acts primarily on Leydig cells, located in the
testicular interstitium; synthesize testosterone
Reflects the parallel rhythyms of FSH and LH levels
o Highest level is found at about 8am
o Lowest level is found at about 8pm
1. Hypergonadotropic hypogonadism
Low testosterone, elevated FSH and LH, and impaired sperm production
B. 5-Reductase Deficiency
Reduction in the levels of 5-reductase – decreased testosterone levels
During puberty, residual enzyme activity sufficiently converts testosterone to
dihydrotestosterone, resulting in development of a male phenotype
C. Klinefelter’s Syndrome
Most common karyotype: 47, XY
Physical manifestations: small and firm testicles, gynecomastia, azoospermia – sterility
D. Myotonic Dystrophy
Testicular failure typically presents in the fourth decade of life
Presents hypogonadism, muscle weakness, frontal balding, muscle dystonia
2. Hypogonadotropic hypogonadism
Low testosterone levels with low or inappropriately normal FSH or LH levels
A. Kallmann’s Syndrome
X-linked recessive trait that manifests as hypogonadism during puberty
Anosmia (inability to smell)
Midline defects (cleft palate and lip)
Certain men also have red-green color blindness, congenital deafness and cerebellar
dysfunction
B. OVARIES
1. ESTROGEN
Principal estrogen: estradiol
Promotes breast, uterine and vaginal development
Responsible for follicular phase changes in uterus
Deficiency would lead to irregular and incomplete development of endometrium
2. PROGESTERONE
Produced by the corpus luteum
Readying the endometrium for embryo implantation
Dominant hormone responsible for the luteal phase
Deficiency would lead to failure of implantation of embryo, thickening of cervical mucus
and reduction of uterine contractions
3. INHIBINS A and B
Produced by the ovaries
Inhibits FSH production
MENSTRUAL CYCLE
2 phases of parallel events occurring at the ovaries and endometrium
Within the ovaries: follicular and luteal phases
Endometrial events: proliferative and secretory phases
A. Follicular Phase
Begins on the onset of menses and ends on the day of LH surge
Early in the follicular phase, the ovary secretes very little estrogen or progesterone
Rise in FSH, however, stimulates estrogen production
Estrogen secreted by the developing follicle within the ovary stimulates:
o Uterine epithelial cells
o Blood vessel growth
o Endometrial gland development to increase the thickness of the endometrium
B. Luteal Phase
Start of the luteal phase is marked by the extrusion of the ovum approximately 36 hours
after this LH surge – luteinization of the Graafian follicle to form the corpus luteum
Corpus luteum secretes progesterone to aid in the implantation of the embryo
In the absence of fertilization, there is gradual decline in the production of progesterone
and estrogen by the corpus luteum, loss of endometrial blood supply, shedding of the
endometrium approximately 14 days after ovulation occurred.
Typical duration of menstrual bleeding: 3 – 5 days ; blood loss averaging 50 mL
Onset of menses marks the end of the luteal phase
1. Amenorrhea
Absence of menses
Primary amenorrhea: has never menstruated
Secondary amenorrhea: at least one menstrual cycle followed by absences of menses for
a minimum of 3 – 6 months
2. Oligomenorrhea
Infrequent or irregular menstrual bleeding
Cycle length in excess of 35-40 days
Menorrhagia – uterine bleeding in excess of 7 days is dysfunctional
HIRSUTISM
Abnormal, abundant androgen-sensitive terminal hair-growth in areas in which terminal hair
follicles are sparsely distributed or not normally found in women
FERRIMAN-GALLWEY SCALE
9 Areas of Assessment:
Lip chin Scale of 1 – 4 based on hair thickness and
Sideburn region pigmentation
Neck
Chest Score of higher than 8 is consistent with a
Abdomen diagnosis of hirsutism
Upper back
Lower back
Upper thigh
Lower thigh
1. Renin
Initial component of renin-angiotensin-aldosterone system
Produced by the juxtagromerular cells of the renal medulla
Responds to decreased extracellular fluid volume and low blood pressure
2. Erythropoietin
Production by cells close to proximal tubules
Production is regulated by blood oxygen levels – hypoxia prodces increased serum
concentration within 2 hours
Acts on the erythroid precursors in the bone marrow
Decreased EPO: Chronic renal insufficiency and anemia
3. 1, 25-dihydroxy Vitamin D3
Active form of vitamin D
Determine phosphate and calcium balance
Bone calcification in the human body
Osteomalacia – inadequate bone calcification; adult form of rickets – distortion of normal
vitamin D metabolism
4. Prostaglandins
↑ Renal blood flow
↑ Sodium and water excretion
↑ Renin release
B. PANCREAS
1. Secretin
Responsible for the production of bicarbonate-rich and alkaline pancreatic fluid
Protects the lining of the intestines from damage
Synthesized in response to the acidic contents of the stomach reaching the duodenum
Activated by gastric activity
2. Cholecystokinin
Formerly called pancreozymin
In the presence of fats or amino acids in the duodenum, is produced by the cells of the
intestinal mucosa
Responsible for the release of enzymes from the acinar cells by the pancreas into the
pancreatic fluid
C. GASTROINTESTINAL TRACT
1. Gastrin
Secreted by specialized G cells in the gastric mucosa and the duodenum
In response to: vaginal stimulation; contact with secretagogues
Inhibitory influences include high gastric acidity
D. PLACENTA
3. Progesterone
Made by the placenta from maternal cholesterol
Helps to maintain the endometrium – promoting growth and thickening of mucosal cells
and adequate uterine blood supply
Decreased progesterone levels leads to fetal demise; poor uterine blood supply (resulting
to endometrial sloughing) and inhibits further ovarian follicle development
4. Estriol
Major estrogen produced by the placenta during pregnancy