Biochem
Pic 1: A 50-year-old woman is evaluated for obesity, hypercholesterolemia, and high LDL cholesterol levels. She is prescribed a drug commonly used to inhibit the rate-limiting enzyme of cholesterol synthesis. If the dashed line in the image represents the enzymatic kinetics of this medication’s target enzyme, which black line represents the anticipated change with the medication?
B. Statins are a reversible competitive inhibitor, causing no change in Vmax, and an decrease in potency.
A 67-year-old man comes to the ED with acute chest pain that began 5 hours ago. ECG shows elevated ST segments in leads I, avL, and V5-V6, Laboratory studies reveal elevated troponin I. He is prepared for coronary artery reperfusion therapy using angiography. Describe what features would be found in the myocardium after the tissue is reperfused, and the cause of these findings.
Contraction bands. Due to sudden influx of intracellular Ca2+ levels in the cell following reperfusion, but a lack of ATP, the myocytes remain stuck in a contracted state, forming dense, dark microscopic bands.
A 34-year-old man with a history of ulcerative colitis is hospitalized after developing intense abdominal pain and passing loose bright red stools. The physician recommends initiating therapy with a drug to reduce inflammation and achieve remission of the patient’s acute flare-ups. Treatment calls for a high dose followed by a slow taper. Which of the following adverse effects is most likely to arise from long-term use of this medication?
A. Adrenal hyperplasia
B. Agranulocytosis
C. Hepatotoxicity
D. Renal toxicity
E. Osteoporosis
E. Osteoporosis – prednisone / corticosteroid use (CUSHINGOID symptoms)
A 45-year-old man with cirrhosis and ascites is being evaluated for worsening lower extremity edema. You are asked to calculate the net fluid movement across his capillaries to understand the pathophysiology of his edema.
Capillary hydrostatic pressure (Pc) = 28 mm Hg
Interstitial hydrostatic pressure (Pi) = -3 mm Hg
Capillary oncotic pressure (πc) = 18 mm Hg (decreased due to hypoalbuminemia)
Interstitial oncotic pressure (πi) = 8 mm Hg
Filtration coefficient (Kf) = 0.5 mL/min/mm Hg
What is the net fluid movement in mL/min & in which direction?
5.5 mL/min filtration (out of capillary)
A 32-year-old woman presents to her physician with a 1-week history of vaginal itching and discharge. The patient is afebrile. Physical examination reveals no abdominal or adnexal tenderness. The cervix bleeds during the collection of fluid with a cotton swab. Speculum examination demonstrates a frothy discharge with a greenish hue. What is the most likely pathogen and what is the test to confirm the diagnosis?
Trichomonas, flagellated organisms on wet mount.
A researcher is studying neurologic disorders by examining the functions of a cellular organelle linked to a myelin synthesis disorder. The researcher finds that, during experiments, the organelle breaks apart very long-chain fatty acids at every second carbon. However, there is no activity when short-chain fatty acids are present.
What is another function of the organelle being researched?
Peroxisomes produce bile acids
A 43-year-old man living with HIV is brought to the physician by his caregiver because of significant cognitive and behavioural decline over the last 6 months. The patient has not had recent fevers, headaches, or motor/sensory changes. Recent CD4+ cell count was 150/mm3. His temperature is 37.0c. The CSF shows HIV viral load of 700copies/mL. Giant cells are found on a specimen from the patient's brain. Explain what the diagnosis is and why giant cells are found.
HIV encephalitis causes infection of the microglia, which fuse to form giant cells.
A 52-year-old man visits his primary care physician because of fatigue. He has a history of hypertension managed with medication. He was recently started on medications for dyslipidemia and type 2 diabetes mellitus. Results of laboratory studies show:
pH: 7.47
Na+: 136 mEq/L
K+: 3.0 mEq/L
Cl−: 95 mEq/L
HCO3−: 31 mEq/L
What class of medication is likely to cause the follow metabolic abnormalities?
Thiazide / Loop diuretic
Both thiazide and loop diuretics commonly cause a hypokalemic metabolic alkalosis as a result of volume depletion and increased potassium and hydrogen ion excretion. The diuretic-induced volume depletion activates the renin-angiotensin-aldosterone system, resulting in increased aldosterone levels. The high aldosterone, plus increased urine flow, also cause the hypokalemia
62-year-old woman is in the ICU following septic shock. You want to assess her tissue oxygen extraction to evaluate end-organ perfusion.
Laboratory and hemodynamic values:
Cardiac output (CO) = 4.0 L/min
Hemoglobin (Hb) = 10 g/dL
Arterial oxygen saturation (SaO₂) = 98%
Mixed venous oxygen saturation (SvO₂) = 58%
What is the patient's oxygen consumption (VO₂) in O2/min?
218 mL O₂/min
VO₂ = CO × Hb × 13.6 × (SaO₂ - SvO₂)
VO₂ = 4.0 × 10 × 13.6 × 0.40
You are in GP and your next patient is a 6-year-old boy presenting with a maculopapular rash. The rash initially began behind the ears before spreading over the whole body. Prior to getting the rash, the mother noticed some white spots in his mouth. The child was also lethargic, irritable and had a fever during this period. Looking at his medical notes, you see that he has not received his vaccinations and he has previously had chickenpox. The most likely causative agent in this child belongs to which of the following families of viruses?
Paramyxoviridae (measles)
What are the 3 components of intercalated discs and their functions?
Fascia adherens connects actin filaments to transmit mechanical force of contraction, gap junctions allows flow of ions, desmosomes connects intermediate filaments to tether cardiac cells together during physical stress. Intercalated discs ensure coordinated/synchronized contraction of cardiac tissue.
A 65-year-old who emigrated from Kenya 3 months ago comes to the emergency department noticing blood in his urine. He denies pain. Examination shows mild hepatosplenomegaly, and urinalysis is positive for RBCs. Cytoscopy shows a large fungating mass adherent to the superior part of the bladder. Results of the biopsy is shown. What risk factors are associated with this disorder (Name 2)?
Schistosomiasis, chronic/recurrent infections (cystitis), long-standing nephrolithiasis,, pelvic radiation.
A 30-year-old man begins working as a nurse and as part of his employment screening has a tuberculosis purified protein derivative test that is positive. He denies cough, fever, and weight loss, and x-ray of the chest is normal. He has a history of injectable drug use and of jaundice. His serum studies show an aspartate aminotransferase of 240 U/L, alanine aminotransferase of 285 U/L, and a positive hepatitis B surface antigen test.
Which antituberculosis medication is safest for this patient?
Ethambutol
(Isoniazid, rifampin-type drugs, and pyrazinamide all may cause hepatitis, with the risk being greater in patients with preexisting liver disease, as seen in this case. Of the tuberculosis drugs, ethambutol and levofloxacin do not commonly cause hepatotoxicity and so would be safest)
The fusion of the trigone and the bladder is formed by the fusion of which embryological layer(s)?
Endoderm + Mesoderm (Intermediate mesoderm)
Trigone = intermediate mesoderms
Bladder = endoderm (hindgut) derived
A 54-year-old gentleman is referred to the neurologist by his GP for progressive gait disturbance over the last few months. He has no significant medical history, but has not been seen by healthcare professionals for many years due to his busy schedule. Upon questioning, he recalls a history of a painless lesion on his penile shaft many years ago, which resolved spontaneously. His family history is non-contributory. He travels often for business, and consumes two glasses of wine a week. He eats a balanced diet. On examination, the patient slams his feet hard onto the ground while walking. There is no past-pointing, dysdiadochokinesis, or nystagmus. His peripheral sensation is intact, and his motor function is normal. On examination of his cranial nerves, small pupils are noted which do not respond to light, but contract normally to accommodation and convergence. Considering the most likely diagnosis, lesions of what anatomic location are contributing to his gait disturbance?
Dorsal column of the spinal cord (tertiary syphilis)
A 71-year-old woman is brought to the ED because of fatigue, dizziness, and palpitations. For the past few months, her diet has consisted of small quantities of coffee, rice crackers, and jelly. Laboratory studies show 10.9g/dL, MCV of 105.9fL. Homocystine levels are elevated, methylmalonic acid levels are normal. What biochemical mechanism is defective?
Transfer of methyl group transfer due to deficient methyl THF
Pic 2: A 68-year-old man has had increasingly severe back pain for 2 months. Hematocrit is 30%. A photomicrograph of bone marrow aspirate is shown. What pathogen is most likely to be associated with complications of this disorder?
Multiple myeloma, encapsulated bacteria: S. pneumo, H. influenzae, N. meningitidis, Salmonella.
A 56-year-old man is evaluated in the hospital for fever, a dramatic increase in leukocyte count, and profuse watery diarrhea. He was admitted 5 days ago when he developed signs of infection and crepitus over the wound site after being stabbed in the right shoulder. He was then started on antibiotics. T38.5°C, pulse: 110/min, respirations are 21/min, and BP 155/95 mmHg. On physical examination, his wound is less erythematic than previously, is not warm to the touch, does not have crepitus, and does not have purulent drainage. His abdomen is tender to palpation. He is given medication to treat his watery diarrhea. The patient is allergic to macrolides.
MOA of most likely medication used for this patient's diarrhea?
Inhibits cell wall peptidoglycan synthesis
(C. diff: Vancomycin inhibits bacterial cell wall peptidoglycan synthesis)
What are the three main structures just outside the carpal tunnel? (That is not a muscle or tendon)
A 68-year-old man with a prosthetic aortic valve presents with 3 weeks of low-grade fever and fatigue. Blood cultures grow gram-positive cocci. Describe the series of test to distinguish the bacteria species.
Catalase test + coagulase test (most likely S.epidermidis)
A 5-month-old is brought to the physician because of a 1-month history of breathlessness and fatigue. Physical examination shows an enlarged tnogue, severe generalized muscular hypotonia, and pitting edema of the extremities. ECG shows short PR intervals with giant QRS complexes. Results of laboratory studies show increased serum creatine kinase and decreased leukocyte acid maltase concentrations. Deficiency of what characterizes the most likely diagnosis in this patient?
Pompe disease: alpha-1,4-glucosidase
Pic 3: A 42-year-old comes to the clinic with 2 days of abdominal pain, fever, and rash. He recently emigrated from China. Temperature is 38.1c, pulse is 102/min, RR is 18/min, BP is 162/98mmHg. On physical examination the patient appears jaundiced. A lacy purple skin discolouration is seen on the lower extremities. Laboratory studies show a creatinine level of 1.6 mg/dL (high), BUN of 22mg/dL (high), presence of HbsAg. What is the diagnosis and what findings would be found in an X-ray angiography of the renal artery?
Bead-like aneurysms ("beads on a string") in kidneys with Polyarteritis Nodosa (PAN)
A 26-year-old gravida 2, para 1 woman at 36 weeks of gestation comes to the office for routine follow-up. She feels well. Two weeks ago, she felt symptoms of a urinary tract infection (UTI) and took sulfamethoxazole-trimethoprim, which she had from a prior UTI. The symptoms resolved in 2 days. The fetal examination and patient examination are normal. Her serum studies show total bilirubin of 5.1 mg/dL and direct bilirubin of 1.1 mg/dL
What damage is the fetus most at risk of?
Neuro- / Cerebral-toxicity OR Basal ganglia damage
(Sulfamethoxazole and other sulfonamides are contraindicated in pregnancy because they bind to albumin and can displace unconjugated bilirubin, leading to cerebral toxicity in the fetus. Kernicterus is characterized by jaundice, lethargy, drowsiness, poor eating habits, fever, spasticity, and opisthotonus. It also can cause cerebral palsy, intellectual disabilities, and hearing and vision loss in the infant.)
1000!!!
A 58-year-old woman with a history of type 2 diabetes mellitus and chronic alcohol use is brought to the emergency department after being found confused at home. Her husband reports she has had severe vomiting and diarrhea for the past 3 days and has been drinking heavily. She has been taking aspirin for chronic back pain. On examination, she is lethargic, tachypneic (respiratory rate 28/min), tachycardic (heart rate 110/min), and hypotensive (blood pressure 90/60 mm Hg). Her abdomen is diffusely tender. She has dry mucous membranes and poor skin turgor.
Laboratory Results:
Qn 1: Is there anion gap?
Qn 2: What is/are the metabolic imbalances here?
Qn 3: Summarize the case we see here.
Qn 1: Yes
Qn 2:
Assess respiratory compensation
Expected PaCO₂ = 1.5 × 16 + 8 = 32 ± 2 mm Hg (range: 30-34 mm Hg)
Actual PaCO₂ = 28 mm Hg (lower than expected)
Delta-delta (Δ-Δ) analysis to detect metabolic alkalosis
ΔAG = 30 - 12 = 18
ΔHCO₃⁻ = 24 - 16 = 8
Δ-Δ = ΔAG - ΔHCO₃⁻ = 18 - 8 = 10
- Delta-delta > 5 indicates a concurrent metabolic alkalosis
- This patient's severe vomiting has caused chloride depletion and metabolic alkalosis
Qn 3:
This patient has a triple disorder: anion gap metabolic acidosis (DKA, lactic acidosis, salicylates, uremia) + metabolic alkalosis (vomiting) + respiratory alkalosis (salicylate-induced hyperventilation). The near-normal pH masks the severity of the underlying disturbances
Pic 1: A 30-year-old woman comes to the emergency department because of a 3-day history of a burning sensation with urination, flank pain, and fever. She has a history of recurrent urinary tract infections. Temperature is 38.3°C (100.9°F), and pulse is 110/min. On examination there is left costovertebral angle tenderness. Urinalysis reveals a pH of 8.5 and is positive for blood, leukocyte esterase, and nitrite. X-ray of the abdomen is shown. What is the likely pathogen?
Proteus mirabilis