• Module 2
  • CBL 8 :

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    CBL 08
    SENARIO:
    A 35- year old man with severe substernal chest pain of about 2 hours duration is brought by ambulance to his local hospital at 5 a.m. The pain is accompanied by dyspnea (shortness of breath), diaphoresis (sweating) and nausea.

    Focused History: The patient reports episodes of exertional chest pain in the last few months, but they were less severe and of short duration. He smokes (2-3 packs per day), drinks alcohol only rarely, eats a “typical” diet, and walks with his wife most weekends. His blood pressure has been normal. Family history reveals that his father and paternal aunt died of heart disease at age 45 years and 39 years, respectively. His mother and younger (age 31 years) brother are said to be in good health.

    Physical Examination (pertinent Findings): The patient is pale and clammy and is in distress due to chest pain. Blood pressure and respiratory rate are evaluated. Lipid deposits are noted on the periphery of his corneas (corneal arcus; see left image) and under the skin on and around his eyelids (xanthelasmas; see right image). No deposits on his tendons (Xanthomas) are detected.

                              

    Task:
    1.    Relative to an individual with familial defective LDL receptors, what would be the expected phenotype in an individual with familial defective apolipoprotein B-100? With apolipoprotein E-2, the isoform that only poorly binds its receptors?

    2.    Why was aspirin prescribed?

    3.    Heart muscles normally uses aerobic metabolism to meet its energy needs. However, in hypoxia, anerobic glycolysis is increased. What allosteric activator of glycolysis is responsible for this effect? With hypoxia, what will be the end product of glycolysis?

    4.    One of the reasons for encouraging smoking cessation and exercise in the patient is that these changes raise the level of HDLs, and elevated HDL reduces the risk for CHD. How does a rise in HDL reduce the risk for CHD?

  • Module 1
  • CBL 7 : Dark Urine and Yellow Eyes

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    CBL 07
    SENARIO:
    A 35-year-old male surgeon presents to his primary care physician with a 2–3-week history of fatigue and right upper quadrant discomfort. During the past week, he has noticed yellowing of his eyes. He was previously healthy and has no chronic medical problems. Several months ago, while supervising a new intern on a trauma case he was accidentally stuck with a needle. He did not seek medical care at that time due to the patient’s critical condition but thinks that the patient may have been a drug user. His physical exam is notable for jaundice, hepatomegaly, and right upper quadrant tenderness and dark urine. His labs include:

    Bilirubin, AST, ALT, Alkaline phosphatase is elevated.

    Learning Objective:
    What is the most likely diagnosis in this patient?

    What are the signs and symptoms associated with this condition that this patient has?

    What is the biochemical basis for yellowing of his eyes and dark urine in this patient?

    What is the biochemical basis for the elevation of aminotransferases in this patient?

    What is the biochemical basis for elevated ALT and AST?

    What type of jaundice is it?

    What is the difference between prehepatic and post hepatic jaundice?

    What is the biochemical basis of jaundice in new born?

  • CBL 6 : Photosensitivity and Skin Blisters

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    CBL 06
    SENARIO:
    A 22 years old male who started working as a laborer comes to the clinic with the complain of skin rash. On examination skin blisters are noted on the sun exposed areas like face and hands. Laboratory evaluation shows elevated total plasma porphyrins and his urine is reddish brown in colour?
    Learning Objective:
    What is the most likely diagnosis?

    Which enzyme is most likely deficient in the patient?

    What is the biochemical basis of elevated plasma porphyrins?

    What is the biochemical basis of skin rash on sun exposed areas?

    What is the biochemical basis of reddish brown colour in the urine?

    What is the mode of Inheritance?

    What are the treatment options?

  • CBL 5: Osteogenesis Imperfecta

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    CBL 05
    SENARIO:
    A 4 years old falls down on the playground and is rushed to the emergency room. Her workup reveals a new fracture in her right tibia, as well as multiple old fractures in her bilateral arms and legs at various stages of healing. On exam, her sclera is blue, hearing loss and dental abnormalities.
    Learning Objective:
    What is the diagnosis?

    What is the mode of inheritance of this disease?

    Comment how the collagen of this boy is affected?

    What is the biochemical basis of blue sclera?

    How to distinguish between child abuse and this disease?

  • CBL 4: Thalassemia

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    CBL 04
    SENARIO:
    A 16-month-old boy present to the clinic with pale skin, failure to thrive and frontal bossing. When the child was born, he was fine and healthy on appearance and examination. Vaccinations till now are up to date. From the last few months parents are noticing paleness and irritability.  On further investigation he was found to have a hemolytic disease, hereditary in nature with synthesis of globin chains defected. On examination hepatosplenomegaly is present.
    Learning Objective:
    What is the likely diagnosis?

    What is the biochemical basis of pale skin?

    What is the biochemical basis of frontal bossing?

    Why the patient is healthy at first and after 1 year he is affected?

    What probable type of mutation is present in the globin chains genes?

    Which sub type of hemoglobin will increase?

    What are the biochemical basis of hepatosplenomegaly?

    What is the possible treatment?

    How the mutation effects its mRNA?

  • CBL 3: Protein Chemistry (Emphysema- α 1 antitrypsin deficiency)

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    CBL 03
    SENARIO:
    A 68-year-old Caucasian man with a 25 pack-year smoking history presented with new-onset dyspnea on exertion in the setting of workplace dust exposure. During his evaluation, he was found to have α1-antitrypsin deficiency with evidence of development of pulmonary emphysema. Workplace spirometric monitoring over 10 years of surveillance for an on-the-job respirator fit program demonstrated a sharp downward slope in forced expiratory volume in one second, or FEV1, during his periods of most significant dust exposure, which was attenuated after discontinuation of his workplace exposure.

    Blood and other body fluids contain a protein, α1-antitrypsin (α1-AT, A1AT, currently also called α1-antiproteinase), that inhibits a number of proteolytic enzymes (also called proteases or proteinases) that hydrolyze and destroy proteins. α1-AT comprises more than 90% of the α1-globulin fraction of normal plasma. α1-AT has the important physiologic role of inhibiting neutrophil elastase ––a powerful protease that is released into the extracellular space, and degrades elastin of alveolar walls, as well as other structural proteins in a variety of tissues. Most of the α1-AT found in plasma is synthesized and secreted by the liver. In the normal lung, the alveoli are chronically exposed to low levels of neutrophil elastase released from activated and degenerating neutrophils. This proteolytic activity can destroy the elastin in alveolar walls if unopposed by the action of α1-AT, the most important inhibitor of neutrophil elastase. Because lung tissue cannot regenerate, emphysema results from the destruction of the connective tissue of alveolar walls. Smoking causes the oxidation and subsequent inactivation of that methionine residue, thereby rendering the inhibitor powerless to neutralize elastase. Smokers with α1-AT deficiency, therefore, have a considerably elevated rate of lung destruction and a poorer survival rate than nonsmokers with the deficiency.

    Learning Objective:
    Fibrous proteins

    Normal structure and synthesis of collagen and elastin

    Abnormalities of fibrous proteins

    Reference Books:
    Lippincott’s textbook of Biochemistry

    Harper’s text book of Biochemistry. (Page 616)

    Davidson’s Practice of Medicine.

  • CBL 2: Protein Chemistry (Creutzfeldt Jakob Disease)

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    CBL 02
    SENARIO:
    A 70 years old man reported for the third time in last 3 weeks in medical OPD with progressive difficulty in walking. He had muscle stiffness, twitching and involuntary jerks in both legs. This patient was being treated by psychiatrists for depression, agitation, mood swings, memory loss and thought problems for 2 weeks immediately preceding the onset of current symptoms. Taking into account the rapid progression and pattern of symptoms he was provisionally diagnosed as a case of Creutzfeldt Jakob Disease. The findings of MRI, EEG and spinal tap were consistent with the diagnosis. Patient was put on supportive symptomatic treatment and relatives were counseled.

    The protein misfolding which is contagious from abnormal to normal protein leads to prion diseases. Prion diseases, such as Creutzfeldt-Jakob disease, occur when prion protein, which is found throughout the body but whose normal function isn’t yet known, begins folding into an abnormal three-dimensional shape. This shape change gradually triggers prion protein in the brain to fold into the same abnormal shape.

    Through a process scientist don’t yet understand, misfolded prion protein destroys brain cells. Resulting damage leads to rapid decline in thinking and reasoning as well as involuntary muscle movements, confusion, difficulty walking and mood changes.

    Learning Objective:
    Chemistry of amino acids

    Levels of protein folding and how it is carried out

    Abnormalities in protein structure/folding

    Reference Books:
    Lippincott’s textbook of Biochemistry

    Harper’s textbook of Biochemistry

    Davidson’s Practice of Medicine

  • CBL 1: Cell (I- Cell Disease- lysosomal targeting problems)

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    CBL 01
    SENARIO:
    A female infant with a normal delivery after 38 weeks and normal intrauterine life showed the physical findings characteristic of I-cell disease. She manifested gargoyle face, progressive psychomotor retardation, and increased serum levels of lysosomal enzymes with decreased activities in peripheral blood lymphocytes. The diagnosis was made by the analyses of lysosomal enzymes. The child died at the age of 2 years and 3 months due respiratory insufficiency. By electron microscopy, various-shaped membrane-bound vacuoles were observed in the cytoplasm of various cells such as hepatocytes, myocardial muscle cells, epithelial cells of renal glomeruli, proximal renal tubular cells, fibroblasts, and chondrocytes. By histochemical analysis we found that these intracytoplasmic storage vacuoles contained glycosaminoglycan and proteoglycan.

    In general, peripheral blood smears are performed to obtain information with regard to various morphological features as an aid in the diagnosis of infection or malignancy. This report presents a patient with I cell disease (inclusion cell disease), a fatal lysosomal storage disorder caused by a defect in an enzyme responsible for the transfer of mannose-6-phosphate ligands to precursor lysosomal enzymes. As A consequence, most lysosomes enzymes are transported outside the cell instead of being correctly targeted into the lysosomes, resulting in the storage of macromolecules in lysosomes. I cell disease, with its heterogeneous clinical presentation, can be diagnosed by the presence of intracellular vacuole like inclusions in lymphocytes and fibroblasts, high serum lysosomal enzyme activities, and a defect of N-acetylglucosamine-1-phospjotransferase. The report describes the morphological aspects of peripheral lymphocytes in a blood smear of a patient, first clue to the final diagnosis of I cell disease. The observed vacuole-like inclusions in lymphocytes of this patient were negative for periodic and Schiff (PAS) and Sudan black B staining, in contrast to earlier reports.

    Learning Objective:
    Structure and function of different organelles of cell.

    Structure, function and pathology of lysosomes.

    Enzyme processing and targeting to organelles.

    Reference Books:
    Lippincott’s textbook of Biochemistry

    Harper’s textbook of Biochemistry

    Davidson’s Practice of Medicine