biochemistry problem set jack blazyk 3/9/04. case #1 lamont
TRANSCRIPT
Biochemistry Problem Set
Jack Blazyk3/9/04
Case #1
Lamont
Presenting Complaint
“I’ve felt so weak lately. Sometimes, I can hardly stand up, and when I do, I feel like I’ll fall,” muttered Lamont.
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 she’s noticed that Lamont is making frequent trips to the bathroom to urinate.
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.
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.
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.
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.
Family Medical History
Lamont’s 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.
Systems Review
• Respiratory
Lamont’s 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.”
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.
Physical Exam
• General Appearance
Height: 71 inches
Weight: 132 pounds
Alert, but disoriented and unbalanced
Thin with poor skin turgor, skin is very dry
Physical Exam
• Vital Signs
Temperature: 101.2°F
Pulse: 115/min supine, 140/min upright
Respirations: 32/min
Blood Pressure: 106/76 supine, 88/60 upright
Physical Exam
• Head / Neck
Mucous membranes red and very dry
Slight superficial cervical and paratracheal lymphadenopathy
• Abdomen
Bowel sounds are hyperactive in all quadrants
Physical Exam
• Neurological
Lethargic, disoriented, and weak, but able to verbalize and communicate
Muscles are very weak
Lab Tests
Acetone Positive
Arterial Blood Gases
P O2 100 mm Hg
P CO2 25 mm Hg
pH 7.18
HCO3- 9 meq/L
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
Lab Tests
Glucose
Random 625 mg/dL
HbA1c 18%
Lab Tests
Lipid Profile
Total Cholesterol 190 mg/dL
HDL Cholesterol 40 mg/dL
LDL Cholesterol 135 mg/dL
Triglycerides 150 mg/dL
Lab Tests
Liver Profile
SGOT (AST) 25 U/L
SGPT (ALT) 39 U/L
Bilirubin 0.8 mg/dL
Lab Tests
Urinalysis
Acetone Positive
Glucose Positive
Questions
1. What is Lamont’s 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?
HyperglycemicConditions
Gly
coly
sis
Glycogenesis
PentoseShunt
Fatty AcidSynthesis
CholesterolSynthesis
TriglycerideSynthesis
Hyperglycemic Liver
Gly
coly
sis Pentose
Shunt
Fatty AcidSynthesis
CholesterolSynthesis
TriglycerideSynthesis
Hyperglycemic Adipose
Hyperglycemic Muscle
Glycogenesis
Insulin-deficientConditions
Liver Glu
con
eog
enes
is
Fatty AcidOxidation
Ketone Body Synthesis
Glycogenolysis
Adipose Fatty AcidOxidation
TriglycerideBreakdown
No Uptake
Muscle Fatty AcidOxidation
Ketone BodyUtilization
No Uptake
Case #2
Mazie
Presenting Complaint
Mazie visits her family practitioner complaining of another yeast infection.
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.
Medication
Mazie takes no prescription or over-the-counter medication on a regular basis.
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.
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.
Past Medical History
Mazie had gall bladder problems 23 years ago.
Past Surgical History
Mazie had her gall bladder removed at age 35.
Family Medical History
Mazie’s 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.
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.
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.
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.
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.
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.
Physical Exam
• General Appearance
Height: 64 inches
Weight: 180 pounds
Alert
Oriented to time, person and place
BMI
Physical Exam
• Vital Signs
Temperature: 98.6°F
Pulse: 80/min supine, 95/min upright
Respirations: 15/min
Blood Pressure: 120/80 supine, 100/60 upright
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
Lab Tests
Acetone Moderate
Arterial Blood Gases
P O2 100 mm Hg
P CO2 32 mm Hg
pH 7.34
HCO3- 17 meq/L
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
Lab Tests
Cardiac Monitor Sinus tachycardia
Lab Tests
Glucose
Random 325 mg/dL
2-hr Postprandial 560 mg/dL
HbA1c 13%
Lab Tests
Lipid Profile
Total Cholesterol 250 mg/dL
HDL Cholesterol 38 mg/dL
LDL Cholesterol 205 mg/dL
Triglycerides 160 mg/dL
Lab Tests
Liver Profile
SGOT (AST) 12 U/L
SGPT (ALT) 15 U/L
Bilirubin 0.4 mg/dL
Lab Tests
Urinalysis
Acetone Negative
Glucose Positive
Questions
1. How does Mazie’s acid-base situation compare to that of Lamont’s? Is Mazie likely to experience full-blown ketoacidosis?
2. How does the root cause of Mazie’s condition compare to that of Lamont’s?
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?
Zimmet et al., Nature 414 (2001) 782
Zimmet et al., Nature 414 (2001) 782
Saltiel & Kahn, Nature 414 (2001) 799
Saltiel & Kahn, Nature 414 (2001) 799
Saltiel & Kahn, Nature 414 (2001) 799
Saltiel & Kahn, Nature 414 (2001) 799
Moller, Nature 414 (2001) 821
Moller, Nature 414 (2001) 821
Statins for the Masses?
Pravachol = pravastatin
Lipitor = atorvastatin
Christopher Cannon, MDBrigham and Women's HospitalBoston, ME
Disclosure: 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 <100 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 <125 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.