Finals Conference

When you’ve worked hard and done well and walked through that doorway of opportunity, you do not
slam it shut
behind you. Reach back; and give others the same chances that helped you succeed
FINALS
BIOCHEMISTRY CONFERENCES
Prepared by: Sec C Batch 2019
Diarrhea – Group 3
Steatorrhea – Group 4
Lactose Intolerance – Group 5
Galactosemia – Group 6
GSD – Group 7 (C2)
GSD – Group 7 (C1)
Glucose 6 Phosphate – Group 8
DM – Group 9
OGTT – Group 9 (C1)
OGTT – Group 10 (C2)
When you’ve worked hard and done well and walked through that doorway of opportunity, you do not slam it shut
DIARRHEA
C1G3: Bonifacio | Bueno | Burton | Busa | Cabezada | Callao
***C2G3: Ortega | Parfan | Paz | Penaflorida | Perez | Perseveranda
1. What is diarrhea? What are the symptoms associated with diarrhea?

Diarrhea is a common condition that involves unusually frequent and liquid bowel
movements. Results from rapid movement of fecal matter through the large intestine.
The large intestine can absorb a maximum of 5 to 8 L of fluid and electrolytes each
day. When the total quantity entering the large intestine through the ileocecal valve or by
way of large intestine secretion exceeds this amount, the excess appears in the feces as
diarrhea.
Symptoms associated with diarrhea:
 a frequent urge to  cramping
evacuate your bowels  bloating
 frequent, loose, watery  dehydration
stools  fever
 nausea  blood in the stool
 abdominal pain
2. What are the common causes of acute diarrhea?
Acute diarrhea is defined as three or more stools per day of decreased form from
the normal, lasting for less than 14 days. Most acute diarrhea or gastroenteritis cases are
caused by enteric infections/ infectious agents. Diarrhea-causing pathogens are usually
transmitted through the fecal-oral route.
The most common cause of acute diarrhea is a viral infection. Other causes include
bacterial infections, side effects of antibiotics, and infections not related to the
gastrointestinal (GI) system
Viruses (e.g., adenovirus, astrovirus, rotavirus, Norwalk virus) are the most
common cause of diarrhea in the United States. The most common ones in children are
rotavirus and in adults are norovirus. Escherichia coli, Clostridium difficile,
and Campylobacter, Salmonella, and Shigella spp. are common bacterial causes. Bacillus
cereus, Clostridium perfringens, Staphylococcus aureus, Salmonella spp., and others cause
food poisoning. Entamoeba histolytica and Giardia, Cryptosporidium, andCyclospora spp.
are parasitic or protozoal agents that cause diarrhea.
Acute watery diarrhea is most commonly seen with traveler's diarrhea caused by
enterotoxigenic E. coli (ETEC), parasite-induced diarrhea
from Giardia andCryptosporidium spp. and, in cases of food poisoning (ingestion of

preformed toxins), from B. cereus and S. aureus.
3. What are the common causes of chronic diarrhea?
If the illness persists for more than 14 days, it is calledpersistent. If the duration of
symptoms is longer than 1 month, it is considered chronic diarrhea.
Lactose intolerance is the cause of chronic diarrhea in some people. Lactose is a
sugar that is contained in cow’s milk. Its proper digestion requires the adequate presence
of an enzyme (lactase) in the wall of the small intestine. Treatment of lactose intolerance
initially involves the elimination of all lactose-containing products from the diet.
Caffeine-containing drinks have a laxative potential. More than two or three cups
of coffee or tea daily can often cause diarrhea. Withdraw gradually over the course of a
few days to avoid headache and try going without for awhile.
Chronic Diarrhea not caused by an infection may result from various causes such
as:
 Disorders of the pancreas (e.g. chronic pancreatitis, pancreatic enzyme
deficiencies, cystic fibrosis)
 Intestinal disorders (e.g. colitis, Crohn’s Disease, irritable bowel syndrome)
 Medications (e.g. antibiotics, laxatives)
 Intolerance to certain foods and food additives (e.g. soy protein, cow’s milk,
sorbitol, fructose, olestra)
 Disorders of the thyroid (e.g. hyperthyroidism)
 Previous surgery or radiation of the abdomen or gastrointestinal tract
 Tumors
 Reduced blood flow to the intestine
 Altered immune function (e.g. immunoglobulin deficiencies, AIDS, autoimmune
disease)
 Hereditary disorders (e.g. cystic fibrosis, enzyme deficiencies)
Case 1: 4. What are the sequence of metabolic changes observed in

diarrhea and correlate these to the clinical manifestations observed in the
patient( gastrointestinal function and motility, alteration in fluid volume,
composition, acid-base bal.)
The patient manifest an infectious type of diarrhea due to virus since no relation
from diet intake was noted. Infectious type of diarrhea affects small and large bowel. The
changes in the small bowel are typically noninflammatory, while the ones in the large
bowel are inflammatory.
As to the alteration of fluid vol. there is no dehydration noted as the patient is well
alert, with good skin turgor and normal urine output. No acid-base imbalance since the
patient was given remedy with the intake of “am” with sugar. Patient may have lost
elctrolytes in the body(Na, K, Bicarbonate) but in insignificant amounts only.
Gastrointestinal function and motility

An excessive number of high amplitude propagating contractions [rapid transit] can
be a cause of diarrhea; it reduces the amount of time food residues remain in the large
intestine for water to be reabsorbed. Changes in the motility of the small intestine may also
occur, but there is little information available on this. Disorders in motility than accelerate
transit time could decrease absorption, resulting in diarrhea even if the absorptive process
per se was proceeding properly.
Alteration in fluid volume & composition
Usually, more than 90% of the fluid entering the small intestine is absorbed, so that
about one litre reaches the large intestine. There, further absorption occurs, only 100 to 200
millilitres of water being excreted each day in formed stools. Any change in the two-
directional flow of water and electrolytes in the small intestine (i.e., increased secretion,
decreased absorption, or both) results in either reduced net absorption or net secretion and
causes an increased volume of fluid to enter the large intestine. When this exceeds its
limited absorptive capacity, diarrhoea occurs.
Absorption of sodium by the villi is impaired while the secretion of chloride in the
crypts continues or is increased. Net fluid secretion results and leads to the loss of water
and salts from the body as watery stools; this causes dehydration.
The small bowel mucosa is a porous epithelium; water and salts move across it
rapidly to maintain osmotic balance between the bowel contents and the blood. Diarrhoea
can occur when a poorly absorbed, osmotically active substance is ingested.
Acid base balance
Metabolic Acidosis
During diarrhea, a large amount of bicarbonate may be lost in the stool. If
the kidneys continue to function normally, much of the lost bicarbonate is replaced
by the kidneys and a serious base deficit does not develop. However, this
compensating mechanism fails when renal function deteriorates, as happens when
there is poor renal blood flow due to hypovolemia. Then, base deficit and acidosis
develop rapidly. Acidosis also results from excessive production of lactic acid when
patients have hypovolemic shock.
Potassium depletion
Patients with diarrhea often develop potassium depletion owing to large
fecal losses of this ion; these losses are greatest in infants and can be especially
dangerous in malnourished children, who are frequently potassium-deficient before
diarrhea starts. When potassium and bicarbonate are lost together, hypokalemia
does not usually develop. This is because the metabolic acidosis that results from
the loss of bicarbonate causes potassium to move from ICF to ECF in exchange for
hydrogen ion, thus keeping the serum potassium level in a normal or even elevated
range. However, when metabolic acidosis is corrected by giving bicarbonate, this
shift is rapidly reversed, and serious hypokalemia can develop. This can be
prevented by replacing potassium and correcting the base deficit at the same time.
5. Evaluate the nutritional status and state of hydration of patient. Compute
for ideal weight for age of the patient.
6-12mos.: Age in months x 500+birth weight(kg)
Patient: 10mos. and 8kg
10mos x 500+3000*=8000g or 8kg . The patient is considered as undernourished for his
age based on the growth and nutritional chart set by WHO (10mos. should have atleast
8.5kg w/ the length of 71.4cm)
6. Determine the adequacy of patient diet before and during diarrhea relate
this to the cycle of malnutrition and diarrhea.
The cycle implies that due to malnutrition the body suffers an immune impaired
system which could cause infectious diseases. In relation during the manifestation of the
disease, the body lacks the ability and capacity to digest, and absorb nutrients which could
cause malnutrition.
7. What biochemical significance if any, can be given to the use of “am”

with sugar in diarrheic patient?
“Am or rice gruel is bland and low in fiber so it cannot disrupt the digestive system. The
water content in rice helps replenish lost electrolytes which are lost in diarrhea.
8. What are the advantages of breastfeeding, use of home fluids or ORS and
other nutritional support for the patient?
 Breast feeding. It reduces the negative effect on episode of the diarrhea on baby’s
growth and nutritional status. It is safe and costs nothing.
 Home fluids and Oral Rehydration. Aims to prevent dehydration and nutritional
damage from diarrhea. During diarrheal episodes a patient could be in danger of
becoming dehydrated so it is advisable to drink plenty of fluids to replace lost
fluids.
Case 2: 9. Dicuss the biochemical basis of diarrhea caused by cholera.
Cholera contains an enterotoxin called choleragen or CT, which is responsible for
the biochemical reaction taken place in the intestines. Once inside the body, it will release
an enterotoxin in the intestine called, choleragen or CT. The structure of choleragen is
composed of two subunits, an A subunit which consists of two domains, A1 and A2 which
is linked by a disulfide linkage and 5 B subunits. Choleragen will bind to the intestinal cell
membrane through the interaction of the B subunit to the GM1 ganglioside receptor on the
membrane resulting to endocytosis of choleragen. Then the A subunit will undergo
cleavage of the two domains, in order for the A1 domain to become active for it will
penetrate the host cell. And so it will activate the target protein, the guanosin 5’-
triphosphate (GTP)-Binding regulatory protein (glycoprotein receptor) associated with
membrane bound adenylate cyclase through an ADP ribosylation reaction. This reaction
will essentially lock adenylate cyclase in its “on mode”, resulting to the excessive
production of cAMP. The high levels of cAMP will activate the cystic fibrosis
transmembrane conductance regulator (CFTR) which will cause massive efflux of ions and
water into the lumen leading to watery diarrhea.
10. What are the clinical manifestations of this type of diarrhea?
The clinical manifestations are severe watery diarrhea that has a milky appearance
that resembles water in which rice has been rinsed in water. Nausea and vomiting occurs
in the early stages of Cholera and dehydration that can develop within hours after the onset
of cholera symptoms. A person would also have symptoms of irritability, lethargy, sunken
eyes, dry mouth, thirst, dry and shirveled skin, litte or no urine output, low blood pressure
and an irregular heartbeat.
11. Is the treatment given to the patient adequate? Discuss the proper
management for diarrhea caused by Cholera.
The treatment given was adequate for the patient because in her case, her degree of
dehydration from cholera was severe. She was cyanotic, had poor skin turgor and low blood
pressure. In her severe state of dehydration, intravenous administration was needed to be
given along with antibiotics as she was very weak. Oral rehydration solution was given
once she able to tolerate to drink. Oral rehydration solution consisting of 3.5g of Sodium
chloride, 1.5 g of Potassium Chloride, 2.9 g of Trisodium Citrate, dehydrate and 20 g of
Glucose Anhydrous. Glucose being the highest amount is needed in order for the rest of
the components to be successfully absorbed by the intestines. Drinking ample amounts of
the solution exceeding her volume of daily stools was able to recovered quickly and
discharge after a week.
STEATORRHEA
***C1G4: Chua | Coronel | Cruz K | Cruz C | Cruz A | Cunanan
C2G4: Prieto | Pua | Punzalan | Quiteves | Quitoriano | Racho
1. What is steatorrhea?
 Steatorrhea is the medical term for fat in stool. Fat in the stool can cause bulky stool
that floats, has an oily or greasy appearance, and smells foul.
 It is caused by malabsorption of fat in the digestive tract
 Temporary steatorrhea may result from dietary changes or intestinal infections.
Steatorrhea that is persistent may result from diseases of the biliary tract, pancreas,
or intestines.
2. How are fats normally digested and absorbed?
 Mouth – mechanical digestion, lingual digestion (lingual lipase) – emulsify fat and
saliva moistens the food to make it easier to swallow
 Stomach – muscles begin to churn and move to further break down food. Once it
leave the stomach, it becomes a semi liquid substance referred to as chyme
 Small intestine – (main absorption for nutrients and digestion of fat)

 Chyme  duodenum, the upper portion of the small intestines
 Cholecystokinin is released by the presence of fat in the duodenum. When it is
released it stimulates the contractions of the gall bladder and common bile duct to
deliver bile in the gut.
 Secretin – secreted in response to the acid in the duodenum. It stimulates the biliary
duct cells to secrete bicarbonate and water, which expands the volume of bile and
increases it flow into the intestine
 Pancreas – secretes bicarbonate ions that neutralize the pH of the chime entering
the small intestine and lipases that break down fat. Bicarbonate makes the
pancreatic secretions alkaline in nature. This flow of alkaline fluid into the small
intestine helps to neutralize the acidic chyme that comes from the stomach.
Neutralizing the acidic chyme provides a better environment for activation of the
pancreatic enzymes. When food enters the duodenum it is deluged with pancreatic juice,
which is defined as an alkaline secretion of the pancreas containing enzymes that aid in the
digestion of proteins, carbohydrates and fats. Because all of the major nutrients are either
completely or partially broken down by enzymes from the pancreas, we see just how vital
this organ is to digestion. This pancreatic juice contains enzymes that complete the
digestion of starch called pancreatic amylase.
Fats are hydrophobic and thus are poorly soluble in the aqueous environment of the
digestive tract. The digestive enzyme, lipase, is water soluble and can only work at the
surface of fat globules. Digestion is greatly aided by emulsification, the breaking up of fat
globules into much smaller emulsion droplets. Bile salts and phospholipids are
amphipathic molecules that are present in the bile.
The hydrophobic (cholesterol portion) and amino acid conjugate is polar and
hydrophilic. The hydrophobic end sticks to each fat molecule and the hydrophilic protrudes
to prevent the molecules from sticking together. The combined structures of fat molecules
and bile molecules are called micelles. Motility in the small intestine breaks fat globules
apart into small droplets that are coated with bile salts and phospholipids, preventing the
emulsion droplets from re-associating.
The emulsion droplets are where digestion occurs. Emulsification greatly increases
the surface area where water-soluble lipase can work to digest TAG. Another factor that
helps is colipase, an amphipathic protein that binds and anchors lipase at the surface of the
emulsion droplet.
Once fat molecules become micelles, lipases go to work, breaking down fat
molecules into fatty acids and monoglycerides, which pass through the small intestine.
After they pass through the small intestine, fatty acids are converted to triglycerides and
free fatty acids, which combine with cholesterol, phospholipids and protein to form a
structure called a chylomicron. The protein coating of the chylomicron makes it water-
soluble so it can travel through the lymph vessels and eventually the bloodstream.
3. What are the abnormalities in digestion and absorption of fats would

cause steatorrhea? Explain the role of the following in the causation of
steatorrhea.
A. enzyme defect –
First group of steatorrhea is the pancreatic deficiency steatorrhea due to the
insufficient production of colipase and lipase to let the normal hydrolysis of lipid
work. It takes place due to chronic pancreatitis and absence of the acinar cells.
Steatorrhea will occur if your body will not be able to absorb all the dietary
fats. In a normal person, when consuming fatty foods, usually the fat is metabolized
by the digestive enzyme called the lipase. Digested fat is then absorbed by your
body. Along with other fat metabolism byproducts (unused) are eliminated in a
form of stool.
Most individuals having cystic fibrosis, the absorption of fats does not work
properly as the disease disrupts the capability of the pancreas to excrete the
digestive enzymes leading to pancreatic insufficiency. If a pancreatic insufficient
patient will eat fatty foods, fat will definitely pass into the digestive tract without
even metabolized and absorbed. It will be mixed with feces as it may travel into
intestines and eliminated like the undigested for.
B. bile deficiency –
Second is the bile salt insufficiency steatorrhea that is due to the failure of
the secretion of bile acids in the circulation.
Steatorrhea may caused by the different biliary tract disorders like the
gallstones and the cholangiocarcinoma which is known as the biliary tract or
gallbladder cancer. The narrowing of the tube (common bile duct) which carries
the bile from your gallbladder and liver into your intestines called as the biliary
stricture can also be one of the causes of steatorrhea. Furthermore, biliary atresia
may cause it also. It is considered present since birth wherein it involves the
collapse of the bile ducts development.
C. integrity of the intestinal epithelium –
Third group group of steatorrhea is the malabsorption steatorrhea which is
due to medications, surgeries and disorders of small intestines.
4. What are the possible complications that may arise from steatorrhea?
Malabsorption of fat soluble vitamins (A,D,E, & K)
 Vit A deficiency causes night  Vit E deficiency causes hemolysis of
blindness. RBC
 Vit D deficiency may lead to  Vit K deficiency causes insufficient
hypokalemia energy and dehydration
5. What are the diagnostic procedures and/ specific symptomatology which can be
used to distinguish the different causes of steatorrhea?
Pancreatic and small intestinal diseases are the major causes of steatorrhea
 Bentiromide test is usually abnormal in steatorrhea due to chronic pancreatitis. In order to
confirm the presence of pancreatic disease, a structural abnormality in the pancreas is
sought by abdominal X-ray (calcification), ultrasound, CT scan, or ERCP.
 D-xylose absorption - when small intestinal disease is suspected as the source of
steatorrhea, function tests of intestinal absorption may be performed.
 The Schilling tests (I and II) and bile acid breath tests assess distal small bowel
function. The Schilling test with antibiotics (part III) and the bile acid breath test will
facilitate a diagnosis of bacterial overgrowth. Structural abnormalities of the small bowel
are detected by barium studies and/or biopsy. Less common causes of steatorrhea require
further diagnostic testing (e.g.duodenal aspiration for Giardia, serum gastrin for Zollinger-
Ellison disease, etc.)
When you’ve worked hard and done well and walked through that doorway of opportunity, you do not slam it shut behind
you. Reach back; and give others the same chances that helped you succeed
Although medications are on the top list for the treatment of steatorrhea, lifestyle changes
can also aid in managing this condition.
 Diet Modification
This is a very important part in the overall treatment of steatorrhea. Before implying
a certain diet to a patient, it is very important to know what the primary cause is, to find
out which diet should be taken.
The most basic and simple of all these treatment under the diet modification is
lessening or decreasing the amount of fat content in one’s diet can facilitate in maintaining
the symptoms under control.
In certain underlying disease for steatorrhea such as the Celiac Disease, aside from
a less fat or fat free diet, the person is also placed on a gluten free diet.
Aside from Celiac disease, vitamin B12 deficiency is somehow linked also as a
cause of steatorrhea and because of that, nutritional support with foods rich in vitamin B12
or vitamin B12 supplements. On the other hand, in such cases where the cause is iron
deficiency anemia or folate / folic acid deficiency then their supplements should be taken
by the patient.
In addition to what was mentioned earlier, pancreatic enzyme replacements or
supplements are also given depending on the underlying medical problem of a patient such
as in the a case of chronic pancreatitis.
 Alcohol Reduction / Cutback

Sometimes, steatorrhea is caused by excessive or heavy alcohol drinking, therefore,
a person’s alcohol intake should be reduced, cutback or even put to an end gradually.
Remember to drink moderately. But in cases where there is a great impairment or serious
disease of the liver or pancreas due to chronic and heavy alcohol drinking, then the person
should slowly withdraw from the alcohol until completely he/she completely stops from
drinking alcohol.
6. How can steatorrhea be managed and prevented?

Prevention of Steatorrhea
Some causes of steatorrhea are primarily due to human lifestyle such as excessive alcohol
drinking, too much fat in the diet, nutritional deficiencies and many more. So if you don’t have
steatorrhea yet, do watch the amount of your alcohol intake and remember to drink moderately. If
you like fatty foods, then try and practice cutting back the portion of what you eat or practice
healthy choices in grocery shopping for food as well as learn to read nutritional labels. For possible
nutritional deficiencies, there are supplements available for this condition.
http://steatorrhea.org/steatorrhea-treatment/
http://www.livestrong.com/article/428367-how-are-dietary-fats-absorbed-into-the-body/
http://www.diagnose-me.com/symptoms-of/steatorrhea.html
https://en.wikipedia.org/wiki/Steatorrhea
http://healthyeating.sfgate.com/fats-digested-8510.html
https://www.youtube.com/watch?v=G_7EchSkkc0
LACTOSE INTOLERANCE
C1G5: Dacio | Dayao | De Jesus | Deperio | Dela Torre
***C2G5: Racines | Ragonjan | Ragpa | Ragragio | Rendon | Renia
1. Review how the body normally digests and utilizes lactose

Lactase enzyme – specifically Lactase- phlorizin hydrolase (LPH) - is normally a part of
the gastrointestinal system’s flora. This enzyme aids in the separation or breakage of glucose and
galactose from lactose, a disaccharide that is essential for nourishment. During consumption of
lactose, lactase enzymes which normally reside in the small intestine, break down lactose into two
simple forms- galactose and glucose. When the breakage is complete, the two components will
be easily absorbed by the intestine and will then be used to either for nourishment or generation of
energy.
2. What are the food sources of lactose?
 Milk Products: Sweetened, condensed milk (15g of lactose), hot chocolate (12g) and goat’s
milk (11g)
 Milk based desserts: Ice milk (9g), ice cream (3-6g) cheese (1g – 3g), whipping cream (3g)
sour cream (4g) and yogurt (4g)
 Additional foods: waffles, pancakes, biscuits, cookies, breakfast cereals, instant potatoes,
soups, potato chips, corn chips margarine and salad dressings
3. Define lactose intolerance. Is it the same as lactase deficiency? How does it

differ from milk allergy?
Lactose intolerance is caused by low levels of the enzyme lactase that your body uses to
break down lactose (milk sugar). While it can produce many distressing and uncomfortable
signals, lactose intolerance is not a true allergy because it does not result in the body developing
an antibody-mediated immune reaction.
True milk allergy, on the other hand, involves a potent immune reaction to specific proteins
in milk. It causes an elevation in various markers of inflammation and heightened immunity.
Though rare, some life-threatening allergic reactions to milk proteins have been reported. Lactose
intolerance causes symptoms of bloating, flatulence, abdominal pain, and watery diarrhea. Milk
protein allergy generally afflicts children and produces symptoms more commonly associated with
allergic reactions, including itching, rash, and wheezing.
4. What are the different types of LI? Differentiate them from one another?
 Primary lactase deficiency: autosomal recessive and also known as adult-type hypolactasia,
lactase non-persistence, or hereditary lactase deficiency. Deficiency of lactase develops at
various ages.
 Secondary lactase deficiency: follows damage to the intestinal mucosa – e.g. acute viral or
bacterial gastroenteritis, uncontrolled coeliac disease or inflammatory bowel disease or
chemotherapy. This resolves when the disease process is over and the intestinal mucosa heals.
It is more common in children and especially in the developing world. The treatment for the
underlying cause usually improves the lactose intolerance.
 Congenital lactase deficiency: an extremely rare autosomal recessive disorder and
associated with minimal or complete absence of, lactase activity. It becomes apparent once
milk is introduced, usually with intractable diarrhea once milk or lactose formula has been
introduced.
 Developmental lactase deficiency: occurs in premature babies (<34 weeks of gestation) and
improves once the intestine matures.
5. What are the characteristic clinical manifestations of lactose intolerance?

Explain the molecular basis behind each symptom
Bloating: undigested lactose in the small intestine draws water and electrolytes out of the
bloodstream by osmosis thus dilating the small intestine causing bloating.
Cramping: The dilated small intestine speeds up the rate of peristalsis producing
cramping. Faster peristalsis means that undigested food moves more rapidly through SI
further impeding normal nutrient absorption.
Flatulence: Once it reaches the large intestine, colonic bacteria attack the intact lactose
and digest it themselves. This process generates odorous hydrogen, methane, and carbon
dioxide, along with short-chain fatty acids
Diarrhea: excess water, gas, and undigested food produce the signature symptom of
lactose intolerance: watery, often “explosive” diarrhea.
6. What laboratory test/ procedures can be done to diagnose large intestine.
Describe each test and give their significance
 Lactose Hydrogen Breath Test (LHBT)
requires you to drink a liquid that contains high levels of lactose. After which, the
amount of hydrogen in your breath at regular intervals is measured. If your body
doesn't digest the lactose, it will ferment in the colon, releasing hydrogen and other
gases, which are absorbed by your intestines and eventually exhaled. Larger than
normal amounts of exhaled hydrogen measured during a breath test indicate that
you aren't fully digesting and absorbing lactose.
 Lactose Tolerance Test (LTT)
This test measures your body's reaction to a liquid that contains high levels of
lactose. Two hours after drinking the liquid, you'll undergo blood tests to measure
the amount of glucose in your bloodstream. If your glucose level doesn't rise, it
means your body isn't properly digesting and absorbing the lactose-filled drink.
 Stool Acidity Test
This test detects lactose intolerance in infants and children. Lactose that is not
absorbed by the small intestine will reach the colon. Colonic bacteria make the stool
acidic
7. Discuss the management for lactose intolerance.

Avoidance of lactose- containing products will relieve the symptoms in most people.
However, minimal amounts of lactose can be tolerated. Supplementation of vitamin D and
consumption of leafy vegetables and fishes as alternative sources of calcium can also be
implemented. Lactase pills can also be one way to manage LI but under keen recommendation of
physicians.
Food Sources of Lactose. 2010. Dieticians of Canada. Retrieved from:
http://www.mountsinai.on.ca/care/fammed/archive/education-and-your-care/patient-resources/nutrition/lactose.pdf Date retrieved: 6 October 2015
Lactose Intolerance. Retrieved from: patient.info/doctor/lactose-intolerance-pro Date retrieved: 6 October 2015
Lactose intolerance. 2015. Mayo Clinic. Retrieved at:
http://www.mayoclinic.org/diseases-conditions/lactose-intolerance/basics/tests-diagnosis/con-20027906 Date retrieved: 6 October 2015
Lancaster, M. Novel Method to Mitigate Lactose Intolerance 2013. Life extension Magazine. Retrieved
at:http://www.lifeextension.com/magazine/2013/11/novel-method-to-mitigate-lactose-intolerance/page-03A Date retrieved: 4 October 2015
Lactose intolerance - Treatment. NHS Choices. Retrieved at: http://www.nhs.uk/Conditions/lactose-
intolerance/Pages/Treatment.aspx Date retrieved: 4 October 2015
Tishkoff, S., Silfen, D., Silfen, L., 2014. Effect of Raw Milk on Lactose Intolerance: A Randomized
Controlled Pilot Study . Annals of Family Medicine. University of Pennsylvania. Date retrieved: 4 October 2015
GALACTOSEMIA
***C1G6: Delos Reyes | Delute | Dionisio | Emman | Fajardo | Feliciano
C2G6: Reyes J | Rivera | Robles | Sabiniano | Sajines
Galactose together with glucose is a monosaccharide constituent of the disaccharide lactose (sugar
found in milk). Lactase is the enzyme responsible for the breakdown of lactose. It is a hexose, C4 epimer
of glucose.Milk products are the main sources of galactose. It can also be obtained from lysosomal
degradation of complex carbohydrates glycoproteins and glycolipid that are important membrane
components.
Galactose Metabolism
1. phosphorylation of galactose
The galactokinase catalyzes the phosphorylation of
galactose using ATP as the phosphate donor to form Galactose-1- phosphate.
2. formation of uridine diphosphate-galactose

Then Galactose-1-phosphate reacts with UDP- Glucose
to produce Uridine diphosphate galactose and glucose-1-
phosphate . The enzyme responsible for this reaction is the galactose-1-phosphate
uridyltransferase(GALT).
3. use of uridine diphosphate-galactose as a carbon source for glycolysis/ gluconeogenesis

UDPGal-4-epimerase converts UDP-galactose to UDP-glucose (C4 epimer). The reaction involves

oxidation and reduction at C4, with NAD as a coenzyme. UDP-glucose can now participate in many
biosynthetic reactions.
This epimerase reaction is reversible (glucose can be converted back to galactose). The UDP-
Galactose can serve as the donor of galactose like in the synthesis of lactose, glycoproteins,glycolipids
and glycosaminoglycans.
If galactose is not provided in the diet(lactose intolerant people), all tissue requirements can be met
by the action of UDP-Gal-4-epimerase.
Synthesis of Lactose
Lactose is a disaccharide (galactose and glucose) with a B1-4 linkage. Also known as milk sugar.
UDP-Gal condenses with glucose to yield lactose which is catalyzed by lactose synthase.
Galactose is needed in our body not only for the formation of lactose (lactation) but as constituent of
glycolipids(cerebrosides), proteoglycans and glycoproteins.
Galactolipids are a class of compounds widely found in the plants and are an important part of the
cell membranes. Galactolipids in plants consists mainly of monogalactosyldiacylglycerols and
digalactosyldiacylglycerols.
Several galactolipids have been shown to possess in vitro and in vivo anti-tumor promoting activity
and anti-inflammatory activity. Like the Dog rose (Rosa canina) it is said to have anti-inflammatory activity
in arthritis.
The galactolipid galactocerebroside (GalC) and its sulfated derivative sulfatide is also in abundance
present in myelin, the membrane around the axons in the nervous system of vertebrates.
Galactose is oxidized as a source of energy

Glycolysis is the conversion of glucose to pyruvate. It has an energy–investment phase and energy–
generation phase with a net of two molecules of ATP.
Galactosemia
Galactose in the blood , an inherited
disorder characterized by inability to utilize
galactose.
Enzymatic defects of galactokinase, galactose-1-
phosphate uridyl transferase and uridine
diphosphate galactose-4-epimerase result in
defective metabolism and accumulation of
galactose and its metabolites causing
galactosemia.
It is included in the newborn
screening,galactosemia with toxic intermediate
metabolic products results in infant failure to
thrive, liver disorders, cataracts and severe
mental retardation.
Galactosemia
 autosomal recessive disorder.
 occurs in approximately 1 of every 60,000 births among Caucasians. The rate is different for other
groups.
Three forms of galactosemia:
 Galactose-1 phosphate uridyl transferase deficiency (classic galactosemia, the most common and
most severe form)
 Deficiency of galactose kinase

 Deficiency of galactose-6-phosphate wpimerase
Symptoms
Infants with galactosemia can develop symptoms in the first few days of life if they eat formula or breast
milk that contains lactose.
Classic and Clinical Variant Galactosemia

 patient with classic galactosemia carries deleterious mutations in both copies of their GALT gene
so that their blood shows essentially no detectable residual GALT activity.
 patient with clinical variant galactosemia also carries deleterious mutations in both copies of their
GALT gene, but one or both mutations leave a small amount of residual GALT activity
What is Galactokinase Deficiency Galactosemia?

 inheritance of deleterious mutations in the human GALK1 gene leading to loss of galactokinase
(GALK) enzyme activity
 patients missing GALK activity cannot fully metabolize galactose so that if they consume a diet
high in lactose/galactose they will accumulate high levels of galactose and galactose metabolites
including galactitol and presumably galactonate, though this metabolite is rarely measured
What is Epimerase Deficiency Galactosemia?

Results from inheritance of deleterious mutations in the human GALE gene leading to partial loss
of UDP-galactose 4’-epimerase (GALE) enzyme activity. Like patients with loss of GALT or GALK
activity, patients with impaired GALE activity cannot fully metabolize galactose.
Patients with impaired GALE activity may be categorized as having one of three forms of
epimerase deficiency: (1) generalized epimerase deficiency which results from profound but not complete
loss of GALE activity, (2) intermediate epimerase deficiency which results from partial but not profound
loss of epimerase activity in multiple tissues, and (3) peripheral epimerase deficiency which results from
loss of epimerase activity only in some cell types (e.g. red blood cells) but not in others (e.g. lymphoblasts
or liver).
Laboratory tests
New Born Screening (NBS)
 a simple procedure done to find out if your baby has a congenital metabolic disorder that may lead
to mental retardation and even death if left untreated.
Galactose Tolerance Test
(Oral and intravenous)
 A liver function test, based on the ability of the liver to convert galactose to glycogen.
 normal value: < 3g present in urine within 5 hrs of 40g of intake.
Beutler Enzyme Spot Test
 Screening test
 Fluorescence indicates the presence of Galactose-1-phosphate uridylyltransferase activity.
Normal : with fluorescence
Galactose-1-PO4 Uridyl Transferase Test (Gal-1-PUT)
 Blood test that measure the level of GALT.
 Normal value: 18.5-28.5 u/g Hb
What is the treatment for galactosemia?

Your baby’s primary doctor will work with a metabolic doctor and a dietitian familiar with
galactosemia to care for your child.
Prompt treatment is needed to prevent serious health problems and mental retardation. Babies with
galactosemia who do not start treatment shortly after birth may have permanent effects.
Infants and children who are either missing the GALT enzyme completely or who have less than 10% of
the normal amount of enzyme must follow a special food plan. They need to avoid all foods with lactose
and galactose. All milk and milk products must be replaced with formula that contains no lactose.
The following are treatments often advised for children with classic galactosemia:
1. Lactose and galactose-free diet:
People with classic galactosemia are encouraged to follow a lactose and galactose-free food plan
throughout life. Lactose or galactose are found in the following foods, all of which must be avoided:
 Milk and all dairy products
 Processed and pre-packaged foods often contain lactose
 Tomato sauces
 Some candies
 Certain medications – tablets, capsules, sweetened liquid drops that

 contain lactose as a filler
 Some fruits and vegetables also contain galactose
 Any foods or drugs which contain the ingredients lactulose, casein, caseinate, lactalbumin,
curds, whey, or whey solids.
Your dietitian will help you develop a food plan that allows your child to avoid lactose and
galactose while still eating the right amount of protein, nutrients and energy to keep him or her
healthy.
Your child’s food plan will depend on many things such as his or her age, weight, general
health, and blood test results. Your dietician will fine-tune your child’s diet over time. The special
food plan should be continued throughout life.
2. Special lactose-free formula

Newborns with galactosemia are given a special formula free of lactose. The most common
formulas used for babies with galactosemia are those made with soy protein isolate.Isomil® and
Prosobee® are two formulas that are made with soy protein isolate. Soy milk itself contains
galactose and should not be used.
Your metabolic doctor and dietitian will tell you what type of formula is best and how much to use.
Some states offer help with payment, or require private insurance coverage for the formula and
other special medical foods.
3. Calcium supplements:
Since children with galactosemia are not eating milk products, calcium intake may be too
low. Therefore, children with galactosemia are often advised to take calcium supplements to ensure
they receive enough calcium each day.
Some doctors also advise Vitamin D and Vitamin K supplements in addition to calcium.
Your doctor will tell you what supplements to give your child and how much. Do not use any
medication or supplement without checking with your doctor.
4. Monitoring health
Babies and young children with galactosemia usually need regular blood and urine tests.
These tests are used to detect toxic substances made when galactosemia is not in good control. The
test results will help your doctors and dietitian fine-tune the treatment to meet your child’s needs.
Your doctor may also suggest a formal evaluation of your child’s mental development and
his or her speech and language skills. If your child shows delays in certain areas of learning or
speech, extra help can be arranged. Early intervention programs are available in most states to
provide services before children reach school age.
5. Informing friend, relatives, teachers and child-care providers

It is important for you to tell everyone who helps care for your child that he or she cannot
eat or drink milk-containing foods. A Medic-Alert bracelet that states your child’s food restrictions
can be helpful. In addition, your doctor may advise you to carry an emergency treatment letter with
steps for your child’s care.
What happens when galactosemia is treated?

Because the body also makes some galactose, symptoms cannot be completely avoided by
removing all lactose and galactose from the diet. Researchers are working on finding a treatment to lower
the amount of galactose made by the body, but there is no effective method to do so at this time.
When treatment starts before a baby is 10 days old, there is a much better chance for normal growth,
development and intelligence. Some children who receive early treatment may have delays in growth but
most attain normal adult heights.
Even with careful treatment from an early age, some children with classic galactosemia show delays
in learning and development and may need extra help in school. Some children develop speech and
language delays. Some have delays in motor skills such as walking and coordination and balance problems.
Some children have behavior changes that may include attention difficulties, low motivation, or
shyness.
Even when carefully treated, girls with galactosemia have a higher chance of having delayed
periods and having premature ovarian failure.
If treatment is started after 10 days of life, delays or learning problems are more likely. The level
of delay varies from child to child. Treatment is still important, even if started late, because it can help
prevent further delays and symptoms.
GLYCOGEN STORAGE DISEASES (C2)

C2G7: Salantes | Sanico | Santos B. | Santos S. | Sarmiento
1. Review the biochemical pathways of glycogenesis and glycogenolysis.

Glycogenesis
As in glycolysis, glucose is phosphorylated to glucose- 6-phosphate, catalyzed by
hexokinase in muscle and glucokinase in liver. Glucose-6-phosphate is isomerized to glucose-1-
phosphate by phosphoglucomutase. The enzyme itself is phosphorylated, and the phosphate group
takes part in a reversible reaction in which glucose 1,6-bisphosphate is an intermediate. Next,
glucose-1-phosphate reacts with uridine triphosphate (UTP) to form the active nucleotide uridine
diphosphate glucose (UDPGlc) and pyrophosphate catalyzed by UDPGlc pyrophosphorylase. The
reaction proceeds in the direction of UDPGlc formation because pyrophosphatase catalyzes hydro-
lysis of pyrophosphate to 2 × phosphate, so removing one of the reaction products. The initial steps
in glycogen synthesis involve the protein glycogenin that is glucosylated on a specific tyrosine
residue by UDPGlc. Glycogenin catalyzes the transfer of a further seven glucose residues from
UDPGlc, in 1 → 4 linkage, to form a glycogen primer that is the substrate for glycogen synthase.
The glycogenin remains at the core of the glycogen granule. Glycogen synthase catalyzes the
formation of a glycoside bond between C-1 of the glucose of UDPGlc and C-4 of a terminal
glucose residue of glycogen, liberating uridine diphosphate (UDP). The addition of a glucose
residue to a preexisting glycogen chain, or “primer,” occurs at the nonreducing, outer end of the
molecule, so that the branches of the glycogen molecule become elongated as successive 1 → 4
linkages are formed. When a growing chain is at least 11 glucose residues long, branching enzyme
transfers a part of the 1 → 4-chain (at least six glucose residues) to a neighboring chain to form a
1 → 6 linkage, establishing a branch point. The branches grow by further additions of 1 → 4-
glucosyl units and further branching.
Glycogenolysis
Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis—the
phosphorolytic cleavage of the 1 → 4 linkages of glycogen to yield glucose 1-phosphate. The
terminal glucosyl residues from the outermost chains of the glycogen molecule are removed
sequentially until approximately four glucose residues remain on either side of a 1 → 6 branch.
The debranching enzyme has two catalytic sites in a single polypeptide chain. One is a glucan
transferase that transfers a trisaccharide unit from one branch to the other, exposing the 1 → 6
branch point. The other is a 1,6-glycosidase that catalyzes hydrolysis of the 1 → 6 glycoside bond
to liberate free glucose. The reaction catalyzed by phosphoglucomutase is reversible, so that
glucose-6-phosphate can be formed from glucose 1-phosphate. In liver, but not muscle, glucose-
6-phosphatase catalyzes hydrolysis of glucose-6-phosphate, yielding glucose.
2. What are the hormones that regulate glycogenesis and glycogenolysis? Explain
the effects of these hormones.
The principal enzymes controlling glycogen metabolism— glycogen phosphorylase and
glycogen synthase—are regulated in opposite directions by allosteric mechanisms and covalent
modification by reversible phosphorylation and dephosphorylation of enzyme protein in response
to hormone action. Phosphorylation of glycogen phosphorylase increases its activity;
phosphorylation of glycogen synthase reduces its activity.
Phosphorylation is increased in response to cyclic AMP (cAMP) formed from ATP by
adenylyl cyclase at the inner surface of cell membranes in response to hormones such as
epinephrine, norepinephrine, and glucagon. cAMP is hydrolyzed by phosphodiesterase, so
terminating hormone action; in liver insulin increases the activity of phosphodiesterase.
Glycogen synthase is the enzyme responsible for adding UDP-glucose to a growing chain
of glycogen. There are two forms of this enzyme. The inactive form is called glycogen synthase b
and it is phosphorylated (P). The active form is called glycogen synthase a and it does not carry a
phosphate group.
The phosphorylation of enzymes is performed by kinases. The complete name of the
enzyme is cyclic AMP-dependent protein kinase A because its activity is regulated by a messenger
molecule known as cyclic AMP (cAMP). Cyclic AMP is made from ATP by the enzyme adenylyl
cyclase and it is degraded by the action of an enzyme called phosphodiesterase
When cAMP is present inside the cell it binds to protein kinase A and activates it so that it
can phosphorylate glycogen synthase. This shuts down glycogen synthesis by deactivating the
enzyme. The key to hormonal regulation is the effect of the hormones on the production of cAMP.
This takes place on the cell surface when the hormone binds to a cell surface receptor molecule.
Insulin, glucagon, and epinephrine are the principal hormones that control glycogen
metabolism in mammals. Insulin, a 51-residue protein is synthesized by the cells of the pancreas.
It is secreted when the concentration of glucose in the blood increases. Thus, high levels of insulin
are associated with the fed state of an animal. Insulin stimulates glycogen synthesis in the liver.
This makes sense since high concentrations of glucose indicate that it's time to store it as glycogen.
Glucagon, a peptide hormone containing 29 amino acid residues, is secreted by the cells of
the pancreas in response to a low blood glucose concentration. Glucagon restores the blood glucose
concentration to a steady-state level by stimulating glycogen degradation. Only liver cells are rich
in glucagon receptors, so glucagon is extremely selective in its target. The effect of glucagon is
opposite that of insulin, and an elevated glucagon concentration is associated with the fasted state.
The adrenal glands release the catecholamine epinephrine (also known as adrenaline) in
response to neural signals that trigger the fight-or-flight response. Epinephrine stimulates the
breakdown of glycogen to glucose 1-phosphate, which is converted to glucose 6-phosphate. The
increase in intracellular glucose 6-phosphate increases both the rate of glycolysis in muscle and
the amount of glucose released into the bloodstream from the liver. Note that epinephrine triggers
a response to a sudden energy requirement; glucagon and insulin act over longer periods to
maintain a relatively constant concentration of glucose in the blood.
Epinephrine binds to β-adrenergic receptors of liver and muscle cells and to α1-adrenergic
receptors of liver cells. The binding of epinephrine to β-adrenergic receptors or of glucagon to its
receptors activates the adenylyl cyclase signaling pathway. The second messenger, cyclic AMP
(cAMP), then activates protein kinase A.
In addition to blocking glycogen synthesis, glucagon and epinephrine stimulate glycogen
degradation. The glycogen degradation enzyme is called glycogen phosphorylase and it comes in
two forms. Glycogen phosphorylase a is the active form and it's phosphorylated (it has an attached
phosphate group). Glycogen phosphorylase b is the unphosphorylated form of the enzyme and it's
inactive.
The phosphorylation of glycogen phosphorylase is carried out by a kinase enzyme. In this
case it's a specific kinase called phosphorylase kinase. Phosphorylase kinase is itself subject to
activation by phosphorylation. The kinase that does this is protein kinase A. Thus, epinephrine and
glucagon will stimulate glycogen degradation in addition to stopping glycogen synthesis.
For every kinase there's a phosphatase that removes phosphate groups from proteins. Recall
that insulin is released when glucose levels in the blood are high. The effect of insulin is the exact
opposite of the effect of glucagon and epinephrine. Insulin binds to a cell surface receptor and
triggers a pathway that leads to activation of protein phosphatase-1. This enzyme dephosphorylates
the three enzymes, glycogen synthase, phosphorylase kinase, and glycogen phosphorylase leading
to activation of glycogen synthesis and deactivation of glycogen degradation. Insulin causes
glucose to be stored as glycogen.
3. Discuss the salient parts of the above case – his manifestations that points out
to a diagnosis of McArdle’s disease, biochemical explanation of the
manifestations, laboratory procedures that were done to confirm diagnosis .
Gerald (Male, 32 year old)
 Chronic arm and leg muscle pains and cramps during exercise
 Muscle weakness in the past
 Muscle pain generally disappeared after 15-30 minutes, and then he could continue his
exercise without any discomfort.
 Elevated serum Creatine kinase during exercise
 During 15 minutes of exercise, blood lactate level is decreased instead of increased.
 High level of glycogen in muscle
Diagnostic procedures
1. Biochemical assay of enzyme 5. Lactic acid test
activity 6. Liver function test
2. Biopsy (Muscle and Liver biopsy) 7. Uric acid- blood test
3. Ischemic forearm test (for GSD V, 8. Triacylglycerol test
VII, X) 9. Creatine phosphokinase test
4. Blood sugar test
Treatment
1. Liver transplantation (GSD IV)
2. Frequent nocturnal gastric feeding to avoid hypoglycemia.
3. Regulating or avoiding strenuous exercise to avoid fatigue symptoms
4. Taking oral glucose or fructose to improve exercise tolerance or injection of glucagon
4. Define glycogen storage diseases. Discuss the different glycogen storage

diseases with emphasis on the following parameters:
A. Type and common name of the glycogen storage disease.
B. Enzyme deficiency or defect
C. Glycogen structure that results
D. Major organs affected
E. Clinical manifestations
F. Diagnostic procedures
G. Treatment
Glycogen storage disease is the result of defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell types.
Glycogen structure
1. Only type 3 and type 4 have abnormal glycogen structure, the rest are normal. GSD III has
short outer chains while GSD IV has long outer chains with short branching points.
Diagnostic procedures
1. Muscle or liver biopsy 5. Genetic testing
2. Blood sugar test 6. Lactic acid blood test
3. Triacylglycerol test 7. Enzyme assay
4. Uric acid- Blood test
Treatment
1. Need frequent feeding overnight to avoid hypoglycaemia
2. Protein supplements for muscle disorder
3. Regulating or limiting strenuous exercise to avoid fatigue symptoms
4. Improving exercise tolerance by oral intake of glucose or fructose or an injection of
glucagon
5. Liver transplantation
GLYCOGEN STORAGE DISEASES (C1)

C1G7: Fernandez | Galolo | Garcia | Guadines | Halili | Ibay
GLYCOGENESIS STEPS IN GLYCOGENESIS

 Synthesis of Glycogen 1. Synthesis of Uridine Diphosphate-
 Occurs in the cytosol glucose (UDPGlc)
 Energy supplied by ATP and UTP 2. Synthesis of a primer to initiate
glycogen synthesis
3. Elongation of glycogen chains by
glycogen synthase
4. Formation of branches in glycogen
GLYCOGENOLYSIS 4. Lysosomal degradation of glycogen

 Degradation of Glycogen  1-3% of glycogen is continuously
 Mobilizes stored glycogen degraded by the lysosomal enzyme, α-
 Not a reverse of glycogenesis 1,4-glucosidase (Acid Maltase).
 Unknown purpose of pathway
STEPS IN GLYCOGENOLYSIS  Deficiency of this enzyme results to
1. Shortening of chains serious Glycogen Storage Disease Type
2. Removal of branches II: Pompe disease
3. Conversion of glucose 1-phosphate to
glucose 6-phosphate
2. Insulin and “Opposing” Hormones control Metabolism.

Insulin is an anabolic hormone, causing cells to store energy substrates at times of excess.
Insulin's action is countered by the catabolic hormones glucagon, adrenalin, noradrenalin and
growth hormone. These act primarily through cyclic AMP (cAMP) and protein kinase A. While
insulin’s actions are quite complex, one can say that the catabolic hormones often work through
activation of protein kinase A with ensuing phosphorylation of key enzymes. Furthermore, insulin
often activates protein phosphatases and initiates dephosphorylation of enzymes involved in
energy metabolism. Some of these are activated by phosphorylation, other are inactivated through
the same mechanism. Insulin activates glycogen synthetase and pyruvate dehydrogenase, and
inactivates phosphofructokinase II and hormone-sensitive lipase. Complicated control mechanism
steer hormone secretion such that phosphorylation of enzymes involved in metabolism is
constantly adjusted to meet energy intake and expenditure, assuring a constant internal milieu.
3. CASE
McArdle’s disease, a type of GSD wherein there is a deficiency of muscle phosphorylase.
The patient had muscle cramps but did not excrete lactate, suggesting a failure to mobilize muscle
glycogen to produce glucose. A muscle biopsy was done and the result showed an unusually high
level of glycogen in the muscle. The reason why he recovers after 15-30 minutes is because of
epinephrine-mediated activation of hepatic glycogenolysis, which provides glucose to the blood
and relieves the failure in muscle glycogenolysis. Treatment of McArdle’s disease usually involves
avoidance of exercise and carbohydrate consumption prior to exercise.
4. Diseases
NAME ENZYME GLYCOG ORGANS MANIFESTATIONS
DEFECT EN AFFECTED
STRUCT
URE
1a ( Von Glucose-6- Normal Liver, kidney Hepatomegaly, retarded growth,
Gierke’s Phosphatase seizures
Disease)
1b Glucose-6- Recurrent bacterial infections
phosphatase
translocase
II (Pompe’s a1,4-Glucosidase or Normal Generalized Cardiomegaly, infantile death
Disease) Acid Maltase but primarily
heart, liver, and
skeletal muscle
IIIa Debranching Shorter Muscle and Hepatomegaly, muscle
(Cori’s/Forb enzyme outer liver weakness, retarded growth,
e’s Disease) (liver and muscle) chains cardiomyopathy
IIIb Debranching Liver Same as IIIa except muscle
enzyme (liver) weakness
IV Branching enzyme Abnormall Liver Cirrhosis, esophageal varices,
(Andersen’s y long ascites
Disease) unbranched
chains
V (Mc Muscle Normal Skeletal Myoglobinuria, muscle cramps
Ardle’s Phosphorylase muscles
Disease)
VI (Her’s Liver Phosphorylase Normal Liver Hepatomegaly, hypoglycemia
Disease)
VII (Tarui’s Phosphofructokinase Normal Muscle Pain and stiffness on exertion
Disease)
IXa Phosphorylase Liver Hepatomegaly, hypoglycemia,
kinase (liver) delay in motor development
IXb Phosphorylase Liver and Hepatomegaly, hypoglycemia,
(liver and muscle) muscle muscle hypotonia
0 Glycogen synthase No hepatomegaly; hypoglycemic
symptoms in morning; growth
delay
G6PD
***C1G8: Iporac | Jamiri | Jayag | Jose | Lara
***C2G8: Sayana | Sepe | Siayngco | Sy | Tacuboy | Tagum
1. Review the Hexose Monophosphate Shunt

Also known as Pentose Phosphate Pathway/ Phosphogluconate Pathway
Alternative route for metabolism of glucose
No ATP formation/ consumption
Takes place in the Cytosol
Two Major Products:
-NADPH- synthesis of fatty acids and steroids
-Ribose- nucleotide and nucleic acid formation
Stages
1 - Oxidative portion of the pathway in which two oxidative reactions provide
NADPH and a hexose is decarboxylated to a pentose.
2 - consists of two reversible isomerization reactions
3 - Non-oxidative portion of the pathway. A series of interconversions of three-
, four-, five-, six-, and seven-carbon sugars
2. Explain the importance of Glucose-6-phosphate dehydrogenase as to the
reaction that it catalyzes and its role in the HMP shunt.
Glucose-6-phosphate dehydrogenase (G-6-PD) catalyzes the initial step in the hexose
monophosphate (HMP) shunt by oxidizing glucose-6-phosphate to 6- phosphogluconolactone and
reducing nicotinamide adenine dinucleotide phosphate (NADP) to NADPH. It is the only source
of NADPH in erythrocytes and main controller of HMP shunt. The NADPH is used in the synthesis
of lipids (lipogenesis): synthesis of fatty acids, cholesterol and other steroids, and in the synthesis
of non-essential amino acids. It protects the membrane of RBCs from the oxidation by keeping the
glutathione in reduce form. The combined effect of HMP shunt to glutathione metabolism is
responsible for protecting intracellular proteins from oxidative stress.
3. Classes
Case belongs to class 3 since hemolysis only occurred in the presence of stressors
4. What is the role of glutathione in the development of hemolytic anemia?

Reduction of glutathione by the NADPH is important to convert hydrogen peroxide and
organic hydroperoxides into stable compounds. Diminished G6PD activity impairs the ability of
the cell to form the NADPH that is essential for the reduction of glutathione and maintenance of
the G-SH pool. This result in a decrease in the cellular detoxification of free radicals and peroxides
formed within the cell. The RBC has no nucleus and mitochondria so it cannot renew its supply of
the G6PD enzyme if it is impaired. Thus, RBCs are particularly vulnerable to enzyme variants
with diminished stability. This leads to increased H2O2 in RBC, decreased life span of RBC,
increased hemolysis, hence causing hemolytic anemia.
5. Medications
6. Explain the mechanism behind the manifestation of Jay R., the patient in the
above case.
The normal synthesis and functioning of the Glucose-6-Phosphate Dehydrogenase enzyme is
essential for the regeneration of NADPH from NADP in the Hexose Monophosphate shunt through
redox reaction. NADPH is found in the Red Blood Cell that reduces disulfide form of glutathione
into its sulfhydryl form, and one of its importance is for the maintenance of the RBC’s structure.
From the case proposed, the deficiency of the enzyme resulted to several manifestations over the
course of the patient’s lifetime.
During the first two days, Jay R. developed jaundice and his unconjugated bilirubin level was
14 mg/dL. One of the clinical manifestations of G6PD deficiency is neonatal jaundice that appears
1 to 4 days after birth. The jaundice evident in the patient resulted from the increased production
of unconjugated bilirubin.
At Jay R.’s 6th year, he had a respiratory tract infection, and his urine was observed to be dark
in color. Jay R.’s respiratory tract infection lead to the destruction of his red blood cells (hemolytic
anemia) causing the dark color of his urine due to the presence of blood. As a sign of the anemia,
his hemoglobin level dropped to 5.4 g/dL as well so he was given a tansfusion of 1 U of packed
red cells.
When the patient reached his 14th year, his anemia was reevaluated and his red cells were found
to be deficient in the enzyme, G6PD. The same manifestations were still observed on the patient
such as mild jaundice, which occurs at certain occasions, and low hemoglobin level accompanied
by the darkening of his urine whenever he had infections.
7.
Semi-quantitative analysis
• Rapid Fluorescent Spot Test
Detects generation of NADPH from NADP
(+) for deficiency if blood spot fails to fluoresce under UV light
• Heinz body examination
Formed particles as a result of irreversible injury by a toxic agent
Evidence of erythrocyte injury, i.e., hemolysis
G6PD + = >30% Heinz bodies
Quantitative analysis
• Spectrophotometric assay
Absorbance at 340 nm given by NADPH formation
Hemolysate is added to a mixture of glucose-6-phosphate and NADP
Normal: 7-10 IU/g Hb at 30 oC
Molecular Diagnosis
• Identification of specific G6PD mutations
• DNA analysis of circulating leukocytes
• Enzyme is under the same genetic control
8. What complications of G^PD deficiency make DNA analysis best for

identification of carriers and patient diagnosis?
9.
Dependent on the clinical syndrome
Hemolytic anemia
Supportive measures (e.g. folic acid, iron supplements, transfusion)
Acute renal failure
Fluid and electrolyte management, Hemodialysis
Neonatal Jaundice
Phototherapy, exchange transfusion
10. Why is it that patients who have G6PD deficiency have lesser tendency to
contract malaria?
Malaria parasites cannot thrive in immature red blood cells. Hemolysis affects mature red
blood cells more readily; there are fewer of them to host malaria parasites. When an infected RBC
dies before the parasite is ready, the malaria parasite dies as well. The cells infected with the
Plasmodium parasite are cleared more rapidly by the spleen.
With the early destruction of red blood cells caused by G6PD deficiency, the asexual intra-
erythrocytic phase of the plasmodium’s life cycle is disrupted.
DIABETES MELLITUS
C1G10: Manuel | Mari | Martin | Matias | Matias | Meija
***C2G9: Tapiador | Tayao | Tolentino | Viacrusis | Viliran | Villaflores
1. What is Diabetes mellitus?

It is a group of metabolic diseases characterized by high blood sugar (glucose) levels, that
result from defects in insulin secretion, or action, or both.
The term diabetes is derived from a Greek word meaning “going through” and mellitus
from the Latin word for “honey” or “sweet.” Diabetes is a disorder of carbohydrate, protein, and
fat metabolism resulting from an imbalance between insulin availability and insulin need.
2. Differentiate the clinical types of DM

CRITERIA DM TYPE 1 DM TYPE 2
Age of onset Childhood / Puberty After age 35
Progress of symptom Rapid Gradual
Nutritional Status at
Frequently undernourished Obesity usually present
onset
Prevalence < 10% of diagnosed diabetes > 90% of diagnosed diabetes
Genetic Predisposition Moderate Very Strong
B cells are destroyed Insulin resistance

Defect / Deficiency
(no insulin) (few insulin)
Frequency of Ketosis Common Rare
Plasma Insulin Low to absent High early in disease
Hyperosmolar Hyperglycemic
Acute Complications Ketoacidosis
State
Response to Oral
Unresponsive Responsive
Hyperglycemic Drugs
Diet, excercise, BP control,

Treatment Insulin is always necessary
Oral Hypoglycemic drugs
3. What is the normal insulin metabolism? Discuss as to its:

a. Biosynthesis
 Insulin is synthesized in significant quantities only in beta cells in the pancreas.
The insulin mRNA is translated as a single chain precursor called
preproinsulin, and removal of its signal peptide during insertion into the
endoplasmic reticulum generates proinsulin.
 Proinsulin consists of three domains: an amino-terminal B chain, a carboxy-

terminal A chain and a connecting peptide in the middle known as the C peptide.
Within the endoplasmic reticulum, proinsulin is exposed to several specific
endopeptidases which excise the C peptide, thereby generating the mature
form of insulin. Insulin and free C peptide are packaged in the Golgi into
secretory granules which accumulate in the cytoplasm.
 When the beta cell is appropriately stimulated, insulin is secreted from the cell
by exocytosis and diffuses into islet capillary blood. C peptide is also secreted
into blood, but has no known biological activity.
b. Release from beta cells of the pancreas

Beta cells in the islets of Langerhans release insulin in two phases. The first phase
insulin release is rapidly triggered in response to increased blood glucose levels.
The second phase is a sustained, slow release of newly formed vesicles that are
triggered independently of sugar.
c. Role in carbohydrate, fat and protein metabolism

 Insulin Promotes Muscle Glucose Uptake and Metabolism
 Insulin Promotes Liver Uptake, Storage, and Use of Glucose
o One of the most important of all the effects of insulin is to cause
most of the glucose absorbed after a meal to be stored almost
immediately in the liver in the form of glycogen. Then, between
meals, when food is not available and the blood glucose

concentration begins to fall, insulin secretion decreases rapidly and
the liver glycogen is split back into glucose, which is released back
into the blood to keep the glucose concentration from falling too
low.
 Insulin Promotes Fat Synthesis and Storage
o Insulin increases the utilization of glucose by most of the body’s
tissues, which automatically decreases the utilization of fat, thus
functioning as a fat sparer. However, insulin also promotes fatty acid
synthesis
 Insulin Promotes Protein Synthesis and Storage.
o Insulin increases the translation of messenger RNA, thus forming
new proteins.
o Over a longer period of time, insulin also increases the rate of
transcription of selected DNA genetic sequences in the cell nuclei,
thus forming increased quantities of RNA and still more protein
synthesis
d. Relationship with glucagon, epinephrine and cortisol

 Glucagon - hormone produced by the A cells of the pancreatic islets. Its
secretion is stimulated by hypoglycemia. In the liver, it stimulates
glycogenolysis by activating phosphorylase. Unlike epinephrine, glucagon
has no effect on muscle phosphorylase. Glucagon also enhances
gluconeogenesis from amino acids and lactate.
 Epinephrine - secreted by the adrenal medulla as a result of stressful
stimuli (fear, excitement, hemorrhage, hypoxia, hypoglycemia, etc) and
leads to glycogenolysis in liver and muscle owing to stimulation of
phosphorylase via generation of cAMP. In muscle, glycogenolysis results
in increased glycolysis, whereas in liver glucose is the main product
leading to increase in blood glucose.
 Cortisol or glucocorticoids are secreted in response to hypoglycemia, and

both inhibit cellular utilization of glucose while promoting fat
utilization, thus increasing gluconeogenesis. This is a result of enhanced
hepatic uptake of amino acids and increased activity of aminotransferases
and key enzymes of gluconeogenesis. In all these actions, glucocorticoids
act in a manner antagonistic to insulin.
4. What is the mechanism behind the development of polyuria, polydipsia and

polyphagia in DM?
Polyuria causes an osmotic diuresis leading to an increased urination. The excretion occurs
when substances such as glucose enter the kidney tubules. The substances cause an increase in the
osmotic pressure within the tubule, causing retention of water within the lumen.
Polydipsia - is a symptom in which the patient displays excessive thirst. They drink large
amounts of water, which raises the pressure of the extracellular medium. The urine produced by
these patients will have a low electrolyte concentration and it will be produced in large quantities
(polyuria).
Polyphagia - excessive hunger and abnormally large intake of solids by mouth. Lack of
glucose to the cells also causes a state of starvation that stimulates the hunger mechanism.
5. What are the diagnostic procedures that can be used to diagnose DM?
Random Blood Glucose Test measures the blood glucose level any time of day without
regard to drinking or eating. This test is sometimes referred to as a random plasma glucose test, or
a casual plasma glucose test.
Fasting Blood Glucose (Sugar) Test is the preferred way to diagnose diabetes. It is easy
to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample
of blood is drawn and sent to the laboratory for analysis. This can also be done accurately in a
doctor's office using a glucose meter.
Oral Glucose Tolerance Test (OGTT) is a gold standard for making the diagnosis of type
2 diabetes. With an oral glucose tolerance test, the person fasts overnight (at least eight but not
more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person
receives 75 grams of glucose (100 grams for pregnant women). Usually, the glucose is in a sweet-
tasting liquid that the person drinks. Blood samples are taken at specific intervals to measure the
blood glucose.
6. What biochemical events lead to the formation of HbA1c (glycosylated

hemoglobin).
Glycation refers to non-enzymatic attachment of sugar to amino groups of proteins.
Glucose sticks to the hemoglobin to make a 'glycosylated haemoglobin' molecule, called
hemoglobin A1C or HbA1C. Once a hemoglobin molecule is glycated, it remains that way. A
buildup of glycated hemoglobin within the red cell, therefore, reflects the average level of glucose
to which the cell has been exposed during its life-cycle. The more glucose in the blood, the more
hemoglobin A1C or HbA1C will be present.
By measuring the HbA1C it can tell you how high your blood glucose has been on average
over the last 8-12 weeks, and the value does not bounce as much as fingerstick blood sugar
measurements. The red blood cells that circulate in the body live for about three months before
they die off. When sugar sticks to these cells, it gives us an idea of how much sugar is around for
the preceding three months.
A normal non-diabetic HbA1C is 3.5-5.5%. In diabetes about 6.5% is good.
7. What are the complications of DM (end organ damage)?

Complications are the result of problems with blood vessels. High sugar levels over a long
time cause narrowing of both the small and large blood vessels. The narrowing reduces blood flow
to many parts of the body, leading to problems.
 Macrovascular (Atherosclerotic Heart disease, Renal Artery Stenosis, Myocardial
Infarction and Sudden Death, Peripheral Vascular Disease, Cerebrovascular Disease)
 Microvascular (Diabetic Retinopathy, Diabetic Nephropathy, Peripheral
Neuropathy, Autonomic Neuropathy, Gastroparesis, Impotence)
8. Discuss the treatment of DM.

o Monitoring blood sugar
 Keep in mind that the amount of sugar in your blood is constantly changing.
Self-monitoring helps you learn what makes your blood sugar levels rise
and fall, so you can make adjustments in your treatment.
o A healthy diet
 To keep your blood sugar at a consistent level, try to eat the same amount
of food with the same proportion of carbohydrates, proteins and fats at the
same time every day.
o Exercise
 Always important, as sedentary lifestyle is always a predisposing factor to
lifestyle diseases.
o Healthy weight
 Being overweight is the greatest risk factor for type 2 diabetes. That's
because fat makes your cells more resistant to insulin.
- Ominous Octet Treatment
 Modifying eating habits and increasing physical activity are typically the
first steps toward reducing blood sugar levels. The patients must be
provided with information on food nutrient content, healthy cooking and
exercise.
OGTT (C1)
C1G9: Lopez | Lucin | Maligang | Mallare | Maltezo | Mante
1. Define random blood sugar (RBS) and OGTT. What is their use in medical
diagnostics?
Random glucose test (aka capillary blood glucose)
a blood sugar test taken from a non-fasting subject. This test, also called random blood
glucose (RBG) or casual blood glucose (CBG), assumes a recent meal and therefore has higher
reference values than the fasting glucose test. A normal blood glucose level reading, without
fasting first, of under 200 mg/dl is considered normal. At that point, if symptoms are present, the
doctor will begin looking at other reasons for the illness. However, a level of over 200 mg/dl,
especially with symptoms of frequent urination, excessive thirst, etc. will indicate a strong
possibility of diabetes.
Oral glucose tolerance test (OGTT)

is determined two hours after drinking a sugar-rich beverage (i.e., one with 75 grams of
glucose), the normal blood sugar or glucose level is below 140 mg/dl. A person with a 2-hour
blood glucose level of 200 mg/dl or over has diabetes, while a person with a value that is 140-199
mg/dl has pre-diabetes. It is recommended for pregnant women who are between 24 and 28 weeks
of pregnancy and for anyone suspected of developing adult diabetes.
2. Enumerate the different steps involved in doing RBS determination and OGTT.
How are the patients prepared before the specimens are collected?
Random Blood Sugar (RBS) - A sample of blood taken at any time can be a useful test if diabetes
is suspected. A level over 200 mg/dl or more in the blood sample indicates that you may have
diabetes. A fasting blood glucose test may be done to confirm the diagnosis.
2-hour glucose tolerance test (GTT) – for this test, the person has a fasting glucose test done
(fasted for at least 8 hours) then drinks a 75-gram glucose drink. Another blood sample is drawn
2 hours after the glucose drink. This protocol "challenges" the person's body to process the glucose.
Normally, the blood glucose level rises after the drink and stimulates the pancreas to release insulin
into the bloodstream. Insulin allows the glucose to be taken up by cells. As time passes, the blood
glucose level is expected to decrease again. When a person is unable to produce enough insulin,
or if the body's cells are resistant to its effects (insulin resistance), then less glucose is transported
from the blood into cells and the blood glucose level remains high.
3. Differentiate between RBS and postprandial blood sugar determination. Which

is better indicator of your blood sugar level? Why?
2-hour postprandial blood sugar
It measures blood glucose exactly 2 hours after you start eating a meal. By this point blood sugar
has usually gone back down in healthy people, but it may still be elevated in people with diabetes.
This is not a test used to diagnose diabetes. This test is used to see if someone with diabetes is
taking the right amount of insulin with meals.
4. Illustrate the normal glucose tolerance curve. Explain the different pints in the
curve and relate them to the different aspects of glucose metabolism.
As demonstrated on the above figure called the glucose tolerance curve, when a normal
fasting person ingests 1 grams glucose/kg of body weight, the blood glucose rises from
90mg/100ml to 120-140mg/100ml and falls back below normal in about two hours.
In person with diabetes, the fasting blood glucose concentration is almost above
110mg/100md and often above 140mg/100ml. This in turn shows an abnormal glucose tolerance
test. On ingestion, people exhibit a much greater tha normal rise in blood glucose and the glucose
level falls back only after 4-6 hours because in type 2 diabetes, there is hyperinsulinemia, however,
there is insulin resistance in the target cells thus impairing carbohydrate utilization and storage,
furthermore, it fails to fall below the control level. The slow fall of the curve and its failure to all
below the control level demonstrate that either (1) normal increase in insulin after glucose
ingestion doesn’t occur or (2) there is decrease in sensitivity to insulin.
DM can be diagnosed on a basis of such a curve and type 1 can be distinguished from type
II by measurements of plasma insulin, with plasma insulin being absent in type 1 and increased in
type II.
5. What is a “prolonged” OGTT curve? What diseases/conditions can bring about

this type of curve?
Prolonged OGTT curve signifies hyperglycemia
Pathologic conditions causing impaired, or diabetic, glucose tolerance results:
* Hypercorticism - curve 5.
* Acromegaly - between curves 4 and 5
* Hyperthyroidism - curve 4.
* Pheochromacytoma (or "emotional hyperglycemia") - between curves 4 and 5
6. What is a “flat” or “inverted” OGTT curve? What diseases/conditions can bring

about such kind of curve?
Flat curve or inverted curve signifies hypoglycemia.
The curve may be flat cause by either technical reason, physiologic or pathological reasons.
Technical reasons might be due to rejection of the glucose administered, timing of blood
withdrawals and assays. It can have a physiologic reason in a sense that it might be due to the
differences between venous and arteriole-capillary blood or pathologic reasons from interaction
with drugs, pituitary, thyroid or adrenal insufficiency and digestive malabsorption. Rapid uptake
of glucose by peripheral tissue results in fasting hypoglycemia. Intestinal malabsorption results in
a minimal increase in serum glucose.
Pathologic conditions causing flat or depressed glucose tolerance results:

 Insulinoma - Curve 2 or even more depressed
 Intestinal malabsorption - curve 2 or even less of an increase
 Low renal glucose reabsorption - may be normal curve 1 or may be depressed as in curve
3
 Hypothyroidism - curve 2.
7. Which test is highly sensitive and diagnostic for Diabetes Mellitus? Why?
The HbA1C test is used to detect type 2 diabetes and prediabetes but is not recommended
for diagnosis of type 1 diabetes or gestational diabetes. The A1C test is a blood test that reflects
the average of a person’s blood glucose levels over the past 3 months and does not show daily
fluctuations. The A1C test is more convenient for patients than the traditional glucose tests because
it does not require fasting and can be performed at any time of the day. The A1C test result is
reported as a percentage. The higher the percentage, the higher a person’s blood glucose levels
have been. A normal A1C level is below 5.7 percent.
OGTT (C2)
C1G10: Villamor | Villanueva | Viquera | Wong | Zaragoza | Zipagan
1) Define random blood sugar (RBS) and OGTT. What is their use in medical
diagnostics?
 It is done to check for diabetes. Monitor treatment of diabetes. Check for diabetes that
occur during pregnancy (gestational diabetes) *GDM is a condition in which women
without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy
(especially during third trimester). Gestational diabetes is caused when the insulin
receptors do not function properly. This is likely due to pregnancy related factors such as
the presence of human placental lactogen that interferes with susceptible insulin receptors.
This in turn causes inappropriately elevated blood sugar levels. A woman has gestational
diabetes when she is pregnant and has any 2 of the following: a fasting plasma glucose of
more than 105 mg/dL, a 1-hour glucose level of more than 190 mg/dL, a 2-hour glucose
level of more than 165 mg/dL, or a 3-hour glucose level of more than 145 mg/dL.
Determine if an abnormally low blood sugar level is present. A test to measure blood levels
of insulin and a protein called C-peptide may be done along with a blood glucose test to
determine the cause of hypoglycemia.
 Random Blood Sugar (RBS)

- It measures blood glucose regardless of when you last ate wherein several random
measurements may be taken throughout the day. Random testing is useful because
glucose levels in healthy people do not vary widely throughout the day. Blood glucose
levels that vary widely may mean a problem. Random testing is not used to diagnose
diabetes.
- No special preparation is required before having a random blood sugar test. Sometimes
blood glucose level is used for screening when a fasting test is not possible, such as
when a person is seriously ill.
 Oral Glucose Tolerance Test (OGTT)

- It is used to diagnose prediabetes and diabetes. It is a series of blood glucose
measurements taken after you drink a sweet liquid that contains glucose. This test is
commonly used to diagnose diabetes in a person who is not pregnant.
It is done to:
a) Check pregnant women for gestational diabetes.
b) Diagnose prediabetes and diabetes.
2) Enumerate the different steps involved in doing RBS determination and OGTT.
How are the patients prepared before the specimens are collected?
 RBS
No special preparation is required before having a random blood sugar test.
Reference Values:
Normal 70-140 mg/dl
Pre-diabetes 140-200 ng/dl
Diabetes 200 mg/dl
However in a random glucose of > 200 mg/dl does not necessarily mean you are
diabetic.
 OGTT
Preparation and Procedure:
1. Before the test
a) Three days unrestricted, carbohydrate rich diet and activity.
b) No medication on the day of the test.
c) 8-12 hours fasting
*The glucose tolerance diagnostic test take up to 4 hours. Since activity can interfere with test
results, the patient will be asked to sit quietly during the entire test results. Do not eat during the
entire test. The patient may dink only water during that time.
2. Blood sample will be collected when the patient arrive. That is the fasting blood glucose
value. It provides a baseline for comparing other glucose values.
3) The patient will be asked to drink a sweet liquid containing a measured amount of
glucose. It is best to drink the liquid quickly. For the standard glucose tolerance test, the
patient will drink 75 grams or 100 grams. Pregnant women drink 75 grams of glucose.
Glucose load: Adult non-pregnant: 75g in 300-400mL of water

Adult pregnant: 100g
Children: 1.75g/Kg body weight
4) Blood samples will be collected at timed intervals of 1, 2, and sometimes 3 hours after
you drink the glucose. Blood samples may also be taken as soon as 30 minutes to more
than 3 hours after the patient drink the glucose (10 minutes before glucose load; 120
minutes after glucose load).
Time of Sample Collection Target Level
Fasting (prior to glucose load) 95mg/dL (5.3mmol/L)
1 hr after glucose load 180mg/dL (10.0mmol/L)
2 hrs after glucose load 155mg/dL (8.6mmol/L)
3 hrs after glucose load 140mg/dL (7.8mmol/L)
3.) Differentiate between RBS and postprandial blood sugar determination. Which
is a better indicator of your blood sugar level? Why?
Difference:
- In RBS, the test can be performed anytime of the day.
- In postprandial blood sugar determination, there is specific time of performing the test
which is exactly 2hours after eating a meal.
Better indicator of blood sugar level:

- The better indicator is postprandial blood sugar determination.
Why?
- The normal range for blood glucose levels two hours after a meal will depend on how
much you last ate. It serves as a test of whether a person may have diabetes, or of
whether a person who has diabetes is successfully controlling their blood sugar. By this
point blood sugar has usually gone back down in healthy people, but it may still be
elevated in people with diabetes.
- Normally, blood glucose levels increase slightly after eating. This increase causes the
pancreas to secrete insulin, which assists the body in removing glucose from the blood
storing it for energy. People with diabetes may not produce or respond properly to
insulin, which causes their blood glucose to remain elevated. Blood glucose levels that
remain high over time may be conclusive if diabetes. Diabetes may be diagnosed if the
2-hour post-prandial blood sugar level is higher than normal for a person’s age. This is
true especially if the test on two different days gives the same results and the person
has symptoms of diabetes.
Healthy adults increase their blood sugar levels by 0.5 mmol/L for every 10 years of life after age
50.
4. Illustrate the normal glucose tolerance curve. Explain the different points in
the curve and relate them to the different aspects of glucose metabolism
A normal glucose tolerance curve has a normal fasting blood glucose or baseline, and a
decline towards controlled level of glucose is seen with 2 hours after last intake of oral solution.
The normal baseline is 90-100mg/dl, as seen in the graph. Then the oral glucose is introduced,
causing a positive deflection in the curve, after 30 minutes to an hour, glucose level is at its peak
and insulin will be exocytose. After two hours, it is expected that the patient will be under
temporary hypoglycemia, and at this point, glucagon will be secreted. When the blood sugar is
normalized, glucagon will stop.
5. What is a prolonged curve? What diseases/ conditions can bring about this type
of curve?
A prolonged curve has an above normal fasting blood glucose level and the decline of glucose
In the blood is slow. This can be seen if the subject is experiencing hyperglycemia, where there is
a rise of glucose present in the blood. Some conditions related are: Cushing's Syndrome,
Acromegaly, Diabetes, Cardiovascular Disease and Obesity.
1. Cushing's Syndrome- excess formation of glucocorticoids (glucocorticoids favors/
stimulates gluconeogenesis)
2. Acromegaly- excess growth hormone
3. decreases sensitiy of tissue to the metabolic effects of insulin
4. Diabetes- inability to produce or lack of insulin
5. CVD, Obesity- increase in visceral fats decrease the number of receptors available for
insulin
6. What is a flat or inverted OGTT curve? What diseases or conditions can bring
about such kind of curve?
An inverted or flat curve is a representation of the patient's condition where there is a
negative deflection of the curve upon intake of oral glucose solution. The conditions that bring
about such kind of curve is: Hypothyroidism and insulinoma.
a. Hypothyroidism- decreased thyroid hormone
- reduced rate of intestinal absorption of glucose
b. Insulinoma
- Hyperinsulinism or increase rate of insulin production due to metastases in the adrenal
gland that causes increased glucose absorption
7. Which test is highly sensitive and diagnostic for diabetes mellitus? Why?
There are different tests to determine and assess if a patient is diabetic or not, namely;
Random Blood Sugar, Fasting Blood Sugar, 2-hr Postprandial Glucose Test, HbA1c, and Oral
Glucose Tolerance Test. The said tests are highly sensitive and diagnostic for diabetes mellitus
except for Random Blood Sugar, because it is only a screening test for D.M., wherein the patient
does not need any preparations or fasting for the procedure to be done, and the blood is collected
at any time of the day.
The true diagnostic and sensitive tests for Diabetes mellitus are FBS, 2-hr postprandial test,
HbA1c, and OGTT, because of the special preparations, procedure, and fasting needed to be done
for the test to proceed.
Fasting Blood Sugar is the common test done to patients for the assessment and diagnosis
of Diabetes mellitus because it is easier to do, and fasting for 8-12 hours is the only preparation
for the patient before drawing a blood sample. FBS is a measure of overall glucose homeostasis.
The reason for fasting is for better analysis of the body’s capability to breakdown glucose to
glycogen (glycogenesis) in the blood by the action of insulin. Food intake results to increase of
glucose and the body regulate the glucose in by releasing insulin in our body, so this sugar in the
blood may be moved into the cells of muscles and other tissues to be used as fuel. And when a
patient has diabetes mellitus, there is decrease secretion of insulin because of progressive
destruction of pancreatic β-islet cells or impaired sensitivity of tissues to insulin action, therefore
resulting to continuous increase of glucose because the insulin does not act on the glucose we
intake or is inadequate in numbers.
Criteria for FBS:
Normal = <100mg/dl
Impaired = 100-125mg/dl
Diabetes Mellitus = ≥126mg/dl
OGTT on the other hand is commonly used to assess patients with Gestational diabetes
mellitus, but may also be used to diagnose patients with diabetes mellitus although it is not
generally recommended. It is a multiple blood sugar test that determines how well the body
metabolizes glucose over a required period of time. The patient is subjected to an unrestricted diet
of 150g of CHO/day for 3days prior to testing, because it is done to stabilize the synthesis of
inducible glycolytic enzymes. With the glucose intake, the patient is examined through his/her
blood glucose results every hour for 3 consecutive hours (3rd hour is optional and usually done if
the 2nd hour is above normal). 2-hr postprandial test is similar with OGTT, the difference between
the two is that this test does not need preparation of patients to undergo a 3-day diet of 150g of
CHO per day, and blood is collected 2 hours after complete meal (75g-100g of glucose)
Criteria for OGTT:
Normal = 2-hr Plasma Glucose <140mg/dl
Impaired = 2-hr PG 140-199mg/dl

Diabetes Mellitus =2-hr PG ≥200mg/dl
GDM patients = 2-hr PG ≥153mg/dl
HbA1c or Glycosylated Hemoglobin is a reliable method in the monitoring of long-term

glucose control. It reflects the average blood glucose level over the previous 2-4 months. It
evaluates diabetic patients if medications, diet and lifestyle are contributing to stabilize the glucose
levels. This test is a monitoring test for diabetes mellitus and is advised to be performed by
individuals with D.M. every 3-6 months. For every 1% change in the test value, 35mg/dl is added
to plasma glucose.
Criteria for HbA1c:
Normal = <5.7%
Impaired = 5.7%-6.4%
Diabeter Mellitus = 6.5% or higher
Experiment: GLUCOSE DETERMINATION

Intended use: For Quantitative Determination of Glucose in serum, plasma and CSF.
Summary and Principle: The accurate estimation of glucose is important in the diagnosis and
management of hyperglycemia and hypoglycemia. Hyperglycemia may occur as a result of
diabetes mellitus, in patients receiving intravenous glucose fluids, during severe stress or as a result
of cerebrovascular accidents. Hypoglycemia may be the result of an insulinoma, insulin
administration, inborn error of carbohydrate metabolism or fasting. The Stanbio single reagent
glucose method is based on a technique described by Trinder et al. Glucose is oxidized in the
presence of glucose oxidase (GOD). The hydrogen peroxide formed reacts, under the influence of
peroxidase (POD), with phenol and 4-aminoantipyrine to form a redviolet quinone complex. The
intensity of the color is proportional to glucose concentration.
β-D-Glucose + H2O + O2 GOD H2O2 + D-Gluconic Acid
H2O2 + 4-Aminoantipyrine + Phenol POD Quinone Complex + H2O
Results: Values are derived by comparing the absorbance of the unknown (u) with that of a
standard (s) identically treated.
Glucose (mg/dL) = Au/As x 100
Where Au and As are the absorbances of unknown and standard, respectively, and 100 the
concentration of standard (mg/ dL)
Expected Values:
Normal Range:
Serum/Plasma = 70 -105 mg/dL, (3.89 – 5.83 mmol/L)
CSF = 40 - 75 mg/dL, (2.22 – 4.17 mmol/L)
Manual Procedure:
1. Remove the amount of reagent to be used for testing and allow warming to ambient
temperature.
2. Glucose reagent is supplied ready-to-use.
3. Zero spectrophotometer at 500 nm with distilled water.
4. For each standard, sample and control, add 1.0 mL reagent to cuvettes/test tubes and warm
to 37°C for 5 minutes.
5. Add 10 μL (0.010 mL) of each sample to its respective cuvette/test tube, mix gently and
return to 37°C incubation.
6. After 5 minutes of incubation, read and record the absorbance of all samples.
Experiment Results
200
180
160 GLUCOSE
140 LEVEL
120
100
80
60
40
20
0
Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 Group 7 Group 8 Group 9 Group 10
Interpretation:
The result of the experiment varies because of the different diet and food intake of each participant.
If we analyse the results with the said normal range of plasma/serum glucose level in the
experiment, the following are normal results: Groups 5, 6, and 8 are the only ones that are in the
range of the normal value and the rest exhibits increased levels of glucose. But in asking majority
of the participants, they stated that they have not undergone fasting before conducting the
experiment and had breakfast before going in to the laboratory. So we can conclude that the reason
for the increased concentration of glucose in the blood of the majority is because of the absence of
fasting in the participants. But if we base the results in the perspective of a RBS testing, all the
results of the participants is within normal range.
*Interfering Substance:
Excessive levels of ascorbic acid can produce falsely low glucose values, because it helps the
body’s cells use up glucose for energy, which helps lower blood sugar level

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 Cortisol or glucocorticoids are secreted in response to hypoglycemia, and

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6. What biochemical events lead to the formation of HbA1c (glycosylated

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Oral glucose tolerance test (OGTT)

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5. What is a “prolonged” OGTT curve? What diseases/conditions can bring about

6. What is a “flat” or “inverted” OGTT curve? What diseases/conditions can bring

Pathologic conditions causing flat or depressed glucose tolerance results:

 Random Blood Sugar (RBS)

 Oral Glucose Tolerance Test (OGTT)

Glucose load: Adult non-pregnant: 75g in 300-400mL of water