chemistry BOC deck Flashcards
(95 cards)
1
Q
Monosaccharides
A
Glucose – Broken down starch
Galactose – Dairy, sugar beets, jams, jelly
Fructose – Fruits, honey
Mannose – Plant polysaccharide, not starch
2
Q
Disaccharides
A
Maltose – Barley, beer, cereals (glu + glu)
Lactose – Milk sugar (glu + gal)
Sucrose – Table sugar, sugar cane, maples (glu + fru)
3
Q
Polysaccharides
A
Starch: plant made
Amylose shorter chains
Amylopectin longer chain with branching
Glycogen: animal made
Similar to amylopectin, but with more branching
4
Q
What does glucose oxidase recognize?
A
β-D Glucose 36%
5
Q
What does glucose form in sugars?
A
Glucose forms ring structure in solution
β-D Glucose 36%
Glucose oxidase recognizes this
α-D Glucose 64%
6
Q
Which hormone lowers blood glucose?
A
Insulin
Secreted by β-islet cells of pancreas
Stimulates movement of glucose into cells
Second Messenger Duties:
1) INCREASE: Lipogenesis, protein synthesis & AA transport, glycogen synthesis
2) DECREASE: Lipase, protein breakdown, gluconeogenesis, glycogenolysis
7
Q
Which three hormones raise blood glucose?
A
Glucagon, Epinephrine, Cortisol, GH, T4, ACTH, and somatostatin.
8
Q
What is the primary hormone responsible for raising blood glucose levels?
A
Glucagon
Secreted by α-islet cell of pancreas
Stimulates glycogenolysis and gluconeogenesis
9
Q
How does epinephrine raise blood glucose levels?
A
Catecholamine secreted by adrenal medulla
stimulates glucagon
release
10
Q
How does cortisol raise blood glucose levels?
A
Secreted by adrenal cortex
Stimulates gluconeogenesis and glucagon release
11
Q
How does growth hormone increase blood glucose levels?
A
Synthesized by Anterior Pituitary
Inhibits glucose uptake by cells
12
Q
How does T4 increase blood glucose levels?
A
Least important, stimulates glycogenolysis
13
Q
How does somatostatin increase blood glucose levels?
A
Secreted by δ-islet cells of pancreas, hypothalamus, and GI tract
Inhibits BOTH insulin and glucagon release
14
Q
How does ACTH increase blood glucose levels?
A
Secreted by Anterior Pituitary
Stimulates cortisol, Insulin antagonist
15
Q
What causes hyperglycemia?
A
High glucose
Resolved by insulin
Pathology: Diabetes Mellitus
Type 1 Absolute Deficiency
Type 2 Resistance with secretory defect
Other
Pancreatic disease, drug/chemical induced etc.
Gestational
Metabolic and hormonal changes during pregnancy
16
Q
Clinical Signs of Diabetes
A
Polyuria
Polyphagia
Polydipsia
Weight loss
Hyperventilation (acetone breath)
17
Q
Polyuria
A
Renal threshold 160-180 mg/dL
18
Q
Polyphagia
A
“Starvation in land of plenty”
19
Q
Polydipsia
A
20
Q
Weight loss
A
“Starvation in land of plenty”
21
Q
Hyperventilation (acetone breath)
A
High ketone level
22
Q
What is the normal range for the fasting blood glucose (8-10 hrs)?
A
Normal 70-99 mg/dL
23
Q
What is the impaied range for the fasting blood glucose (8-10 hrs)?
A
Impaired 100-125 mg/dL
24
Q
What is the diabetes range for the fasting blood glucose (8-10 hrs)?
A
Diabetes ≥126 mg/dL
25
What is the normal range for the 2-hour Glucose Tolerance (OGTT) (8-10 hrs fast)?
Normal ≤140 mg/dL
26
When do you see a peak in the 2-hour glucose tolerance test?
Usually time of peak after meal
27
What is the impaired range for the 2-hour Glucose Tolerance (OGTT) (8-10 hrs fast)?
Impaired 140-199 mg/dL
28
What is the diabetic range for the 2-hour Glucose Tolerance (OGTT) (8-10 hrs fast)?
Diabetes ≥200 mg/dL
29
What are the doses for the OGTT?
50g Gestational screen
75g 2 hr OGTT
100g Women who failed first gestational screen, 3 hour challenge
30
How does the three-hour challenge work if you fail the first gestational screen?
3 hour challenge: 2 of these true for diagnosis
FBS ≥95 mg/dL
1 hr ≥180 mg/dL
2 hr ≥155 mg/dL
3 hr ≥140 mg/dL
31
5 hr GTT
Testing for reactive (postprandial) hypoglycemia
Will see large drop (40 mg/dL or more)
32
Which test reflects average glucose over 2-3 months
Hemoglobin A1c
Average lifespan of RBC 120 days
Test reflects average glucose over 2-3 months
Diabetes ≥6.5%
Hemoglobinopathies will interfere
33
Which test reflects average glucose over 2-3 weeks?
Fructoasmine
Glucose attaches to other proteins too!
2-3 week period, NO FRUCTOSE INVOLVED!
34
What is a product of insulin production?
C-peptide
A product of insulin production
Absent in type 1 diabetes
35
What is produced more in type 1 than type 2 diabetes?
Ketones
78% BHB, 2% acetone, 20% AAA
Produced more in type I diabetes (DKA)
36
Write out the hexokinase reaction.
At what wavelength does the absorbance increase at?
Hexokinase (reference)
Glucose + ATP
(HK, Mg2+)------->
Glucose−6−phosphate + ADP
Glucose−6−Phosphate + NADP
(G−6−PDH)--------->
6−phosphogluconate
+ NADPH
Increase in absorbance at 340 nm
37
What is used to measure the glucose oxidase reaction?
What does the glucose oxidase test measure?
Write out the reaction for glucose oxidase.
Glucose Oxidase
From here can measure with polarographic electrode
Measures O2 consumption, must sequester H2O2
β−D Glucose + O2
(GO)-------->
Gluconic Acid + H2O2
38
What is the trinder reation?
Trinder Reaction
H2O2+4−aninophenazone + phenol
(peroxidase)------->
Quinone Complex + 2 H2O
Many interferences
39
What is another method of measure glucose oxidase?
Chromogenic Oxygen receptor, or dye that changes color in presence
of H2O2
40
Write out the glucose dehydrogenase reaction?
At what wavelength does the absorbance increase at?
Glucose Dehydrogenase
β−D Glucose+NAD
(GDH)------>
D−glucono δ lactone+NADH+H+
Patented Rxn, only 1% of labs use
Increase in absorbance at 340 nm
41
Mutarose coverts?
If glucose is in the name, it is specific for β−D Glucose
Mutarose coverts α to β
42
Galactose
Galactosemia: failure to thrive
Deficiency in 1 of 3 enzymes for galactose metabolism
Usually galactose-1-phosphate uridyltransferase
Diarrhea, vomiting
Mental retardation (DD) and catarats if untreated
Screened for at birth
43
Microalbumin
Diabetes causes damage to the kidney
Early sign is increase in urine albumin
Microalbumin is not a small molecule of albumin!
44
Porphyrins
* Chemical intermediates of heme synthesis
* Hemoglobin, Myoglobin, Cytochromes
* Iron captured to form heme
* Heme + Proteins = hemoprotins
45
What are the characteristics of porphyrins?
* Stable compounds
* Color
* Red-violet, red-brown
* Fluoresce when stimulated @ 400 nm
46
3 clinically important compounds
* Protoporphyrin- excreted in feces
* Uroporphyrin-excreted in urine
* Coproporphyrin- excreted in either!
47
Reduced porphyrins are?
Porphyrinogens (the actual
building blocks)
48
What are the characteristics of prophyrinogens?
* Unstable
* Colorless
* No flourescence
* Readily oxidized to porphyrins by light, O2 or oxidizing
agents
49
Why do we look for porphyrins over prophyrinogens?
porphrins are stable and prophyrinogens are unstable.
50
Acquired or inherited enzyme deficiency
* In Bone Marrow: Erythropoeitic
* In Liver: Hepatic
Early precurors:
* Abdominal pain
* neuro-psych
* vomiting
* constipation
* tachycardia
* fever
* leukocytosis
* parastheia
Late precursors:
* Skin manifestations:
* blisters
* facial hair
* photosensitivity
* hyperpigmentation
51
Inherited Porphyrias
* Autosomal dominant inheritance
* ADP and CEP are autosomal recessive
* Decrease in enzyme activity leads to build-up of
precursor molecule
* The level of activity left is enough to make the heme
needed to prevent anemia
52
Inherited ALA Dehyratase Deficency Porphyria
* Inherited ADP
* 7 cases in the entire world, the ultimate zebra
* Urinary ALA↑↑↑
* PBG Norm
* Coprophorphyrin III ↑-urine
* Lead also decreases ALAD funtion
* Adding dithiothreitol restores their ALA function
53
Acute Intermittent Porphyria (AIP)
* HMBS deficincy
* Crisis often precipitated by drugs
* Urine ALA ↑
* Urine PBG↑
* Urine turns red-brown on standing
* Delayed by refrigeration, protection from light, pH
preservation.
54
* Congenital Erythropoetic Porphyria (CEP)
* Uroporphyrinogen III cosynthase deficiency
* Appears shortly after birth
* Red-brown urine staining diaper
* Teeth fluoresce red under UV (stained red-brown)
* Photosensitivity
55
* Porphyria cutanea tarda (PCT)
* Deficiency of Uroporphyrinogen decarboxylase (UROD)
* Most common porphyria
* Blistering and fragility in light-exposed areas
* Urine Uroporphyrin↑ hepatocarboxylic porphyrin↑
isocoproporphyrin↑
* Will be resolved with low dose chloroquine and iron
depletion
* Hepatoerythropoeitic porphyria more or less same
* Has increased ZPP
56
PCT type 1
* Type I: Limited to liver no family history
57
PCT type 2
*Type II: In all tissue, autosomal dominant
58
Hereditary Coproporphyria (HCP)
* Deficencey of coproporphyrinogen oxidase (CPOX)
* Urine & Feces ↑↑Copro III
* Can be precipitated by drugs, hormones, nutritional
changes
* Mild neurological and photosensitive symptoms
59
Variegate Porphyria (VP)
* Prevalent in South Africa thanks to two Dutch people
* Protoporphyrinogen oxidase activity decreased
* Neurologic dysfuntion
And/Or
* Photodermatitis
* Fecal Copro↑ Proto↑↑
60
Erythropoeitic Porphyria (EP/EPP)
* Ferochelatase the enzyme that puts the iron in heme
* Photosensitivity present from infancy
* Burning, itching, pain on exposure
* Liver concequences
* RBCs Proto↑
* Greatly varied presentation
61
Watson-Schwartz & Hoesch screening tests
* PGB forms red-orange when mixed with Ehrlich’s
reagent
* P-dimethylaminobenzaledhyde
62
Watson-Schwartz uses chloraform or butanol extraction
* If cherry-red remains in aqueous phase + for PBG
63
Hoesch test
In Hoesch test there is no reaction with urobilinogen
64
Why do porphyrins fluoresce better in acidic solutions?
* After being extracted, ultraviolet light reveals pink or
red fluorescence
* They may be read quantitatively due to fluorescence
peaks
* 400-405nm and 594-598nm
* Standards are used to calibrate curve
* Each solvent has its own wavelengths in different
solvents
65
* Zinc Protoporphyrin
Metabolite formed when Zn not Fe gets into
protoporphyin
* If Iron cannot get into the ring, the zinc is used instead
* Will also increase in iron-deficiency anemia
* Whole amount not usually reported, usually in ratio to
normal heme
66
* Heme synthesis interfered with
Similar symptoms
* Anemias, liver disease, lead, alcohol can cause
* In 2º Porphyrias Urinary ALA↑ BUT PGB Normal
* Lead poisoning will also have RBC ZPP ↑
* Assay for lead is still better way to detect
67
Draw out Porphyrin Synthesis. What is the rate controlling step?
68
Evelyn Malloy
bilirubin combines with diazotized sulfanilic acid to
form azobilirubin (purple)
69
How does the Jendrassik-Grof modify the evelyn Malloy test?
Jendrassik-Grof modifies this by shifting pH at end to make
azobilirubin blue
Only able to combine with water soluble bilirubin (direct)
Measuring all bilirubin requires solubilizing
Accelerant
70
Direct Bilirubin
Water-soluble
Reacts readily
with diazo
reagent
71
Indirect
bilirubin
Lipid-soluble
Reacts with
diazo after
adding
accelerant
72
Total
Bilirubin
Assay with diazo
and accelerant
After doing total
and direct, can
calculate indirect
73
Jaundice- Not a disease
Yellowing due to high amounts of bilirubin, eye sclera/conjunctiva
first
74
What causes pre-hepatic jaundice?
overwhelm liver processing
75
What causes hepatic jaundice?
liver function impaired
76
What causes post-hepatic-jaundice?
plumbing backs up
77
Kernicterus
Unconjugated bilirubin overwhelms albumin
Lipid soluble, makes it to brain, damages newborn brain
Results in developmental disability, can be fatal
78
Prehepatic
Jauncidce
Due to increased RBC turnover
Hemolytic anemias
Liver usually able to keep up
Keeps levels below harmful levels, <5 mg/dL
Circulating bilirubin is unconjugated (indirect)
79
Hepatic
Jaundice
Bilirubin metabolism or transport is impaired
Bilirubin builds up, unconjugated (usually)
80
Which disease is a partial loss of UDPGT?
Gilbert’s disease
81
Total loss of UDPGT
Crigler-Najjar
82
Which disease prevents secretion into canaliculi?
Dubin-Johnson syndrome
83
Rotor syndrome
Unknown etiology, similar to D-J
84
Post-Hepatic
Jaundice
Also known as obstructive jaundice
Gallstones, tumors, inflammation, even liver flukes may block bile
duct
Liver able to conjugate and secrete but it never gets past
gallbladder
No pigments in feces = clay colored stool
Backup causes regurgitation into bloodstream
Lots of conjugated/direct bilirubin present
85
What is a key symptom/clinical sign of post-hepatic jaundice?
No pigments in feces = clay colored stool
86
When is bilirubin a problem?
Phototherapy
87
Typical testing patterns of pre-hepatic jaundice
Total bilirubin
Normal / Increased
Unconjugated
bilirubin
Increased
Urobilinogen
Increased
88
Typical testing patterns of hepatic jaundice
Total bilirubin:
Increased
Conjugated bilirubin
Normal / Increased* /
?Decreased?
Unconjugated
bilirubin:
Increased
urine color:
Dark
Alkaline phosphate
levels:
Slight elevation
AST & ALT levels:
Increased
89
Total bilirubin
Increased
Conjugated bilirubin
Increased
Urobilinogen:
?Decreased? /
Negative
Urine color:
Dark
Stool colour:
pale
Alkaline phosphate
levels:
increased
90
Alkaline phosphate
levels
Hydrolase that breaks down starch and glycogen
– Requires Cl- and Ca2+ activators
– Acinar cells of pancreas and salivary glands are sources of amylase
■ Smallest enzyme, found in urine
■ Salivary amylase deactivated by stomach
– Acute pancreatitis
- AMY rises in 5-8 hours, peaks @ 24, and normal at 3-5 days
91
How do we measure amylase?
■ Somogyi Units
– Specifically amount of reducing sugar liberated (multiple products)
– U/L with our own ref. range
■ Measurement Methods
– Separate out salivary with
wheat germ lectin
– Immunoassay for specific
Isoenzymes
■ Macroamylasemia: benign
92
Lipase (LIPA/LPS)
Hydrolyzes ester bonds to produce alcohol and fatty acids
– Specifically partially hydrolyzes triglyceride into 2-monoglyceride and 2 fatty
acids
– Pancreatic lipase is specific for the fatty acids at positions 1 & 2
■ Substrate must be emulsified to occur, bile salts and colipase accelerate
■ Lipase is primarily found in pancreas
– Specific for pancreas!
– Increases 4-8 hours after acute pancreatitis
– Peaks at 24 hours
– Normal at 8-14 days
■ Longer lasting marker for pancreatitis
93
How do we measure lipase?
Assay
– Early method Cherry-Crandall used olive oil to measure
– Turbidimetric assay sees decrease in turbidity caused by fats
– Colorimetric also based on glycerol kinase coupled reaction
94
Pancreatitis
Exocrine secretions digest foods
– Safeguards prevent activation of enzymes
– Intrapancreatic secretion and activation
■ “autodigestion”
■ Precipitated by alcohol abuse, gallstones, trauma, [extremely] high triglycerides
– Treatments usually supportive
– TPN only has given way to EN (Enteral Nutrition)
95
Alkaline phosphatase (ALp)
Group of enzymes that catalyze hydrolysis of phosphomonoesters at
alkaline pH
– Liberates inorganic phosphate from organic molecule
– Production of alcohol as a result
– Optimal pH 9-10 but varies with substrate
■ Requires Mg2+ as activator
■ Present on most cell outer surfaces
– Liver, bone, spleen, intestine, placenta and kidneys are highest
