Biochemistry Problem Set

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Biochemistry Problem Set

• Jack Blazyk
• 3/9/04

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Case 1

• Lamont

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Presenting Complaint
Ive felt so weak lately. Sometimes, I can
hardly stand up, and when I do, I feel like Ill
fall, muttered Lamont.
4
History of Chief Complaint
Lamont, a 15-year-old boy, presents in the
emergency department with general weakness that
has increased progressively over the past three
weeks. He states that he thinks he has had the
flu. He admits nausea, fever, and abdominal pain
as part of his flu symptoms. He also states that
although he often feels hungry, he has had
trouble eating. He has had some diarrhea and
flatus. He denies any vomiting. He denies any
history of head injury . Mom says shes noticed
that Lamont is making frequent trips to the
bathroom to urinate.
5
Medication
Lamont takes no prescription or over-the-counter
medication on a regular basis, except for an
occasional Advil for sports-related aches and
pains.
6
Habits
Lamont denies recreational drug use. He does not
use tobacco or alcohol. He had been exercising
regularly in high school athletics until about 3
months ago, when he began to feel worn out and
decided to take a break.
7
Social History
Lamont lives at home with his parents and younger
brother and attends high school. Until recently,
he was active in wrestling and track.
8
Past Medical History
Lamont has had no major medical problems in the
past, except for a case of pneumonia when he was
six years old.
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Family Medical History
Lamonts father, 45 years old, has hypertension
as does his paternal grandfather. The father, a
local landscaper, says that his only sibling, a
brother, had a wasting type sickness as a young
boy and that he died at age 10. Except for
fibrocystic breast disease, the mother is in good
health. Her parents died in a plane crash in
1969. There is no family history of heart
disease, high blood pressure, stroke, renal
disease, tuberculosis, cancer, psychiatric or
neurological disorders, migraine headaches, blood
diseases, rheumatic disease or gout.
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Systems Review

• Respiratory
• Lamonts mother states that he had pneumonia when
  he was 6 years old and that he has had a fever
  off and on for the last couple of weeks, but she
  doesn't know how high.
• Gastrointestinal
• Lamont complains of some abdominal pain and has
  had nausea and diarrhea with his flu.

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Systems Review

• Endocrine
• Lamont admits to frequent trips to the bathroom
  during the day and having to get up during the
  night as many as five or six times to urinate.
  He states that he has been drinking quite a bit
  of water for the past few months now, and that he
  has lost about 25 pounds in the last 6 months,
  which he attributed to not eating right and loss
  of appetite.

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Physical Exam

• General Appearance
• Height 71 inches
• Weight 132 pounds
• Alert, but disoriented and unbalanced
• Thin with poor skin turgor, skin is very dry

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Physical Exam

• Vital Signs
• Temperature 101.2F
• Pulse 115/min supine, 140/min upright
• Respirations 32/min
• Blood Pressure 106/76 supine, 88/60 upright

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Physical Exam

• Head / Neck
• Mucous membranes red and very dry
• Slight superficial cervical and paratracheal
  lymphadenopathy
• Abdomen
• Bowel sounds are hyperactive in all quadrants

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Physical Exam

• Neurological
• Lethargic, disoriented, and weak, but able to
  verbalize and communicate
• Muscles are very weak

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Lab Tests
Acetone Positive Arterial Blood Gases P O2 100
mm Hg P CO2 25 mm Hg pH 7.18 HCO3- 9 meq/L
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Lab Tests
Electrolytes Na 148 meq/L K 5.4
meq/L Cl- 103 meq/L HCO3- 9 meq/L Anion gap 41
meq/L
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Lab Tests
Glucose Random 625 mg/dL HbA1c 18
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Lab Tests
Lipid Profile Total Cholesterol 190 mg/dL HDL
Cholesterol 40 mg/dL LDL Cholesterol 135 mg/dL
Triglycerides 150 mg/dL
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Lab Tests
Liver Profile SGOT (AST) 25 U/L SGPT (ALT) 39
U/L Bilirubin 0.8 mg/dL
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Lab Tests
Urinalysis Acetone Positive Glucose Positive
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Questions

1. What is Lamonts acid-base situation? How did
   this arise?
2. What is happening in adipose cells? How is this
   regulated?
3. Since glucose can enter liver cells by
   facilitated diffusion, why is the liver NOT
   capable of reducing the blood glucose
   concentration?
4. What is happening in skeletal muscle? Why?
5. What is HbA1c and what is its significance? Is
   hemoglobin the only protein that can react with
   glucose?

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HyperglycemicConditions
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Hyperglycemic Liver
Glycogenesis
Glycolysis
Cholesterol Synthesis
Pentose Shunt
Triglyceride Synthesis
Fatty Acid Synthesis
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Hyperglycemic Adipose
Pentose Shunt
Glycolysis
Cholesterol Synthesis
Triglyceride Synthesis
Fatty Acid Synthesis
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Hyperglycemic Muscle
Glycogenesis
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Insulin-deficientConditions
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Liver
Glycogenolysis
Gluconeogenesis
Ketone Body Synthesis
Fatty Acid Oxidation
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Adipose
No Uptake
Triglyceride Breakdown
Fatty Acid Oxidation
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Muscle
No Uptake
Ketone Body Utilization
Fatty Acid Oxidation
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Case 2

• Mazie

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Presenting Complaint
Mazie visits her family practitioner complaining
of another yeast infection.
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History of Chief Complaint
Over the years, Mazie, a 58-year-old female, has
experienced recurring yeast infections. This is
her fourth this year. She states she has been
thirsty lately and urinates frequently. She says
that she is hungry all the time. Recently, she
has noticed that she gets dizzy when she stands
up quickly.
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Medication
Mazie takes no prescription or over-the-counter
medication on a regular basis.
35
Habits
Mazie has smoked two packs of cigarettes a day
for over 30 years. She admits to an occasional
beer. Her lifestyle is totally sedentary.
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Social History
Mazie is a housewife with six children, ages 28
to 42. She lives in Nelsonville with her
husband, who is unemployed. She has never been
outside of Athens County in her life, and has
only been to Athens twice. She worries whether
Medicaid will cover her doctor bills.
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Past Medical History
Mazie had gall bladder problems 23 years ago.
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Past Surgical History
Mazie had her gall bladder removed at age 35.
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Family Medical History
Mazies maternal grandmother had sugar and died
at age 64. Her mother, age 73, also has sugar
and has had two heart attacks, the most recent
last year. Her father died in an accident at the
coal mine when she was 2. Her only sibling, a
57-year-old sister, has sugar and kidney problems.
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Systems Review

• Cardiovascular
• Mazie admits dyspnea on exertion, but denies any
  recurrent chest discomfort, palpitations,
  orthopnea, paroxysmal nocturnal dyspnea,
  hypertension, edema, cyanosis, cardiac murmurs,
  phlebitis, varicosities or claudication.

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Systems Review

• Respiratory
• Mazie often has coughing spells upon waking in
  the morning, but denies any history of pain in or
  unusual drainage from the ears, nose or throat.
  She does not suffer frequent nosebleeds. She
  denies recurrent chest pain, wheezing,
  hemoptysis, pneumonia, tuberculosis, fever or
  night sweats.

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Systems Review

• Gastrointestinal
• Mazie admits to increased appetite recently. She
  denies any history of recurrent abdominal pain,
  chronic indigestion, pyrosis, food dyscrasias,
  anorexia, recurrent nausea, vomiting, diarrhea,
  constipation, hematemesis, abnormal stools,
  jaundice, hemorrhoids or recent change in bowel
  habits.

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Systems Review

• Urinary
• Mazie admits to a burning sensation on the
  outside while urinating. She admits to
  polyuria, and has to get up three or four times
  at night to urinate. She denies any problems
  with urinary urgency, dysuria, hematuria, facial
  edema, oliguria, recurrent kidney or bladder
  infections, difficulty starting urinary stream,
  change in size or force of urinary stream, kidney
  stones, incontinence or urinary retention.

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Systems Review

• Genital / Reproductive
• Mazie has experienced repeated yeast infections
  accompanied by cheesy white discharge.
• Endocrine
• Mazie admits to dry skin and increased thirst and
  urination recently. Over the past two years, she
  has gained about 20 pounds.

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Physical Exam

• General Appearance
• Height 64 inches
• Weight 180 pounds
• Alert
• Oriented to time, person and place

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BMI
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Physical Exam

• Vital Signs
• Temperature 98.6F
• Pulse 80/min supine, 95/min upright
• Respirations 15/min
• Blood Pressure 120/80 supine, 100/60 upright

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Physical Exam

• Head / Neck
• Mucous membranes dry and pink
• Dentition is poor, with numerous caries noted
• Gingiva are inflamed
• Genitals
• White cheesy discharge (KOH positive) noted

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Lab Tests
Acetone Moderate Arterial Blood Gases P O2 100
mm Hg P CO2 32 mm Hg pH 7.34 HCO3- 17 meq/L
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Lab Tests
Electrolytes Na 140 meq/L K 4.2
meq/L Cl- 100 meq/L HCO3- 14 meq/L Anion
gap 30 meq/L
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Lab Tests
Cardiac Monitor Sinus tachycardia
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Lab Tests
Glucose Random 325 mg/dL 2-hr Postprandial 560
mg/dL HbA1c 13
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Lab Tests
Lipid Profile Total Cholesterol 250 mg/dL HDL
Cholesterol 38 mg/dL LDL Cholesterol 205 mg/dL
Triglycerides 160 mg/dL
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Lab Tests
Liver Profile SGOT (AST) 12 U/L SGPT (ALT) 15
U/L Bilirubin 0.4 mg/dL
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Lab Tests
Urinalysis Acetone Negative Glucose Positive
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Questions

1. How does Mazies acid-base situation compare to
   that of Lamonts? Is Mazie likely to experience
   full-blown ketoacidosis?
2. How does the root cause of Mazies condition
   compare to that of Lamonts?
3. Is Mazie producing insulin? If so, how much?
4. From the diagnostic studies, estimate how long
   Mazie has been experiencing these symptoms.
5. How will the long-term treatment differ for Mazie
   compared to Lamont?

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Zimmet et al., Nature 414 (2001) 782
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Zimmet et al., Nature 414 (2001) 782
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Saltiel Kahn, Nature 414 (2001) 799
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Saltiel Kahn, Nature 414 (2001) 799
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Saltiel Kahn, Nature 414 (2001) 799
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Saltiel Kahn, Nature 414 (2001) 799
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Moller, Nature 414 (2001) 821
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Moller, Nature 414 (2001) 821
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Statins for the Masses?
Pravachol pravastatin Lipitor atorvastatin
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                            Christopher Cannon, MDBrigham and Women's HospitalBoston, MEDisclosure Research grant support Bristol Myers Squibb, Merck, Sanofi-Synthelabo Consultant AstraZeneca, GlaxoSmithKline, Guildford Pharmaceuticals, Vertex
Pravastatin or Atorvastatin Evaluation and
Infection Therapy-Thrombolysis in Myocardial
Infarction 22 (PROVE IT-TIMI 22) Lipid-lowering
therapy with statins has been problem to reduce
the risk of cardiovascular events, but the
optimal degree of low-density lipoprotein (LDL)
cholesterol lowering isa unclear. PROVE IT was
designed to answer to assess whether 1) statins
are effective in reducing cardiac events when
started early after acute coronary syndromes, and
2) intensive lowering of LDL cholesterol confers
added benefit compared with LDL cholesterol
lowering to lt100 mg/dL as recommended by current
national guidelines. PROVE IT was conducted at
349 sites worldwide and included 4,162 patients
who had been hospitalized for an acute coronary
syndrome (ACS) within the previous 10 days. They
were randomized to intensive lipid-lowering
therapy with atorvastatin, 80 mg/day, or a
moderate-intensive strategy with pravastatin, 40
mg/day. The primary endpoint was the composite of
all-cause mortality, myocardial infarction,
documented unstable angina requiring
hospitalization, revascularization, and stroke.
The mean duration of treatment and follow-up was
2.5 years, at which time 1,001 total events were
recorded. To be eligible, patients had to be in
stable condition and had to have a total
cholesterol 240 mg/dL, measured within the first
24 hours after the onset of ACS (or up to 6
months earlier if no sample had been obtained
during the first 24 hours). Sixty-nine percent of
the study patients had a percutaneous coronary
intervention in response to their ACS. Ninety
three percent of the patients received aspirin
during the treatment period, 69 received ACE
inhibitors, 85 were treated with beta blockers,
and 72 received clopidogrel or ticlopidine
initially (20 at 1 year). The median baseline
LDL cholesterol was 106 mg/dL in each group at
the time of randomization, which was a median of
7 days after the onset of the index event. The
mean achieved LDL cholesterol was 62 mg/dL in the
patients assigned to atorvastatin vs. 95 mg/dL in
those assigned to pravastatin. The primary
endpoint occurred in 22.4 of patients randomized
to atorvastatin and 26.3 of patients assigned to
pravastatin, which corresponds to a 16 risk
reduction (p 0.005) in the atorvastatin
recipients. The benefit of the intensive
lipid-lowering strategy emerged as soon as 30
days and was maintained over time. There was a
trend toward a reduction in all-cause mortality
with the aggressive lipid-lowering strategy (28
relative risk reduction p 0.07). The benefit of
the aggressive strategy was consistent across all
endpoints, except for stroke, and all subgroups.
The benefit of intensive lipid lowering was
greater in patients with a baseline LDL
cholesterol 125 mg/dl compared with patients
with a baseline LDL cholesterol lt125 mg/dL. In
conclusion, PROVE IT demonstrated a benefit to
aggressive LDL cholesterol reduction on top of
optimal management when initiated at discharge in
patients hospitalized for ACS. The results
suggest that after an ACS, the target LDL
cholesterol may be lower than current guidelines,
especially in those patients with higher baseline
LDL cholesterol levels.