Question 1.
A 3 day old infant presents to your office with significant rectal and umbilical site bleeding. Otherwise he has no other symptoms. His mother who accompanied him was proud that she had delivered him at home with the aid of a midwife. There were no complications during pregnancy or delivery. His Apgar scores were 9 at 1 minute and 5 minutes. Since the delivery, the baby has been breast feeding well and has not required any hospital or health care visits. What is the best treatment of the patient’s symptoms?
Platelet transfusions
Platelet transfusions are likely unnecessary as the patient had no other signs of thrombocytopenia, and the vitamin K shot should resolve the bleeding symptoms.
IVIG (Intravenous immunoglobulin)
Pediatricians have used IVIG on the first day of life in children with hemolytic disease of the newborn, but this is unlikely to be the cause of this patient’s symptoms and presentation.
Vitamin K shot
Major takeaway
Vitamin K is given to most children born in the hospital immediately after birth to prevent early deficiency related bleeding. With the increase in home-birthing and other methods and an increased aversion to “vaccines” (which vitamin K is obviously not) in children, more children are not receiving this preventative injection at birth.
Main explanation
Newborn infants who are born at home and are exclusively breast fed are at increase risk of vitamin K deficiency. Hence, most infants are typically given Vitamin K at birth to prevent any deficiency related bleeding complications. However, since the patient was born at home, he did not receive the Vitamin K shot. Classic vitamin K deficiency develops within the first week of life and is characterized by cutaneous, gastrointestinal, umbilical and circumcision-site bleeding in neonates. Though infants who are exclusively breast fed are at risk for iron deficiency, this tends to take more time to develop. Furthermore, Vitamin K shot should be the first line of treatment.
ron supplements
Iron supplements are unlikely to resolve the situation, as unlikely to be microcytic anemia.
Vitamin B1 supplements
B1 supplements are unlikely to help resolve the situation as B1 deficiency presents with hoarseness, anorexia ,restless, aphonea and beri beri.
Question 2.
A 36-year-old man comes to the clinic because of progressive swelling in all of his limbs for the past month. He initially thought that he had been consuming too many salty foods, but the swelling has worsened despite restricting sodium in his diet. His current medications include ibuprofen for chronic back pain. His temperature is 37.0°C (98.6°F), pulse is 83/min, respirations are 16/min, and blood pressure is 138/86 mm Hg. Physical examination shows a palpable liver edge 2cm below the right costal margin and anasarca. Laboratory blood studies are positive for the presence HBsAg and negative for Anti-HBsAg. Urinalysis shows 4+ protein and a follow-up 24-hour urine collection shows a loss of 4.1g of protein. A kidney biopsy is performed and shows thickened capillaries and glomerular basement membrane on light microscopy with subepithelial deposits seen on electron microscopy. Which of the following is the most likely diagnosis?
Alport syndrome
Alport syndrome is an X-linked genetic condition characterized by a defect in type IV collagen production that results in the splitting of the glomerular basement membrane in addition to sensorineural deafness and visual deficits.
Focal segmental glomerulosclerosis
Focal segmental glomerulosclerosis is the most common cause of nephrotic syndrome in Hispanics and African-Americans. Light microscopy shows segmental sclerosis and hyalinosis of glomeruli while electron microscopy shows effacement of foot processes.
Membranous glomerulonephritis
Major takeaway
Membranous glomerulonephritis, also called membranous nephropathy, is the most common cause of primary nephrotic syndrome in Caucasian adults. It is characterized by the deposition of immune complexes between the epithelial cells of the renal tubules (podocytes) and the glomerular basement membrane; thus the complexes are referred to as subepithelial deposits.
Main explanation
Membranous glomerulonephritis, also called membranous nephropathy, is the most common cause of primary nephrotic syndrome in Caucasian adults. It is characterized by the deposition of immune complexes between the epithelial cells of the renal tubules (podocytes) and the glomerular basement membrane, and thus the complexes are referred to as subepithelial deposits. Histological examination with light microscopy will show thickened capillaries and glomerular basement membrane (due to the inflammation caused by the immune complexes). In addition, excess glomerular basement membrane is grown between the immune complexes, producing a “spike and dome” appearance on electron microscopy. These immune complexesproduce a granular appearance on immunofluorescence staining. Usually, the cause of the condition is idiopathic, but it is also associated with hepatitis B, hepatitis C, solid tumors, lupus, or drugs (e.g., penicillamine, NSAIDS, and gold).
Minimal change disease
Minimal change disease is the most common cause of nephrotic syndrome in children. Light microscopy shows normal glomeruli(hence the disease naming) while electron microscopy shows effacement of foot processes. It responds very well to treatment with corticosteroids.
Poststreptococcal glomerulonephritis
Poststreptococcal glomerulonephritis is a cause of nephritic syndrome that presents 2-3 weeks following a skin or pharyngeal infection with group A streptococcus. Symptoms include cola-colored urine, periorbital edema, and hypertension.
Question 3.
A 45 year-old male with a long-standing history of schizophrenia refractory to many medications and frequent psychiatrichospitalizations is started on clozapine. Which laboratory value must be monitored frequently in patients on this drug?
Liver function tests
Liver function tests do not need to be routinely checked in patients on clozapine.
Thyroid function tests
In patients on lithium, thyroid function tests should be monitored since lithium can cause hypothyroidism. However, this is not the case for patients on clozapine.
Kidney function
In patients on lithium, kidney function should be followed routinely to ensure proper clearance of the medication. However, this is not the case for patients on clozapine.
Complete blood count (CBC)
Main explanation
Clozapine is associated with an increased risk of agranulocytosis. Due to this side effect, patients on the medication must be registered in a registry. For the first six months of therapy, the white blood cell count must be checked weekly with CBCs. From 6 months to 1 year, CBCs must be checked every two weeks. After one year, if numbers are stable, CBCs can be checked monthly.
https://www.clozapineregistry.com/Table1.pdf.ashx
Major Takeaway:
Clozapine is associated with an increased risk of agranulocytosis. For the first six months of therapy, the white blood cell count must be checked weekly with CBC
Correct
Clozapine can cause agranulocytosis so a CBC should be done routinely in patients on this medication.
Question 4.
An 80-year-old man comes to the office because of worsening swelling in both his legs. He complains of fatigue, decreased appetite, recent weight loss, and abdominal pain. A CT scan is obtained and shows a large mass on the liver. Which of the following tumor markers would be elevated in this patient to support the most likely diagnosis?
α-fetoprotein (AFP)
Major takeaway
α-fetoprotein is a tumor marker that is elevated in hepatocellular carcinoma (HCC). Symptoms of HCC include anorexia, bloating, weight loss, and peripheral extremity swelling.
Main explanation
Risk factors for malignant hepatoma, also known as hepatocellular carcinoma (HCC), include any chronic inflammation of the liver caused by hepatitis B or C, alcohol, non-alcoholic steatohepatitis, and hemochromatosis. The tumor marker that is associated with hepatocellular carcinoma is α-fetoprotein (AFP). This protein is normally expressed during fetal development and is thought to act as a fetal albumin. While not all patients with hepatocellular carcinoma express AFP, it can be used in those who do express it to monitor treatment response and disease progression.
CA 19-9
CA 19-9 is a tumor marker used for the evaluation of pancreatic cancer. The patient’s history and symptoms suggest hepatic rather than pancreatic malignancy since the latter is associated with a non-tender, enlarged gall bladder.
CA-125
CA-125 is a tumor marker for epithelial carcinoma of the ovary or fallopian tube. It is used for monitoring response to therapy rather than for screening.
Carcinoembryonic antigen (CEA)
Carcinoembryonic antigen (CEA) is a protein normally found in embryonic and fetal tissue. Certain malignancies cause an elevation in CEA, most notably mucinous cancers of the gastrointestinal tract such as colorectal cancer.
S-100
S-100 is an immunohistochemical marker present in cells derived from the neural crest. It is a sensitive marker of melanocytedifferentiation and is elevated in melanomas, schwannomas, and neurofibromas
Question 5.
A 26-year-old man comes to the office because of visual changes for a day. He says he developed a black spot in his eye which progressed to a “black cigar shape” by the next morning. Medical history is non-contributory. Visual examination shows central monocular vision loss. Brain MRI shows ovoid periventricular plaques. The patient is referred to a neurologist who diagnoses the “most common and least aggressive” form of this disease. Which of the following forms of the disease was most likely diagnosed?
Progressive-Relapsing
A rare form of multiple sclerosis (5%), progressive-relapsing multiple sclerosis is characterized by a steadily worsening disease state from the beginning, with acute relapses but no remissions, with or without recovery
Relapsing-Remitting
Major takeaway
Relapsing-remitting multiple sclerosis (RRMS is the most common form of multiple sclerosis(MS). About 85% of people with MS are initially diagnosed with RRMS. People with RRMS have temporary periods called relapses, flare-ups or exacerbations, when new symptoms appear.
Main explanation
Relapsing-remitting multiple sclerosis (RRMS is the most common form of multiple sclerosis(MS). About 85% of people with MS are initially diagnosed with RRMS. People with RRMS have temporary periods called relapses, flare-ups or exacerbations, when new symptoms appear.
Multiple sclerosis (MS) is an autoimmune inflammatory disease in which myelin in the brain and spinal cord are damaged. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may go away completely; however, permanent neurological problems often occur, especially as the disease advances.
There is no known cure for multiple sclerosis. Treatments attempt to improve function after an attack and prevent new attacks. Medications used to treat MS while modestly effective can have adverse effects and be poorly tolerated. Life expectancy is 5-10 years lower than that of an unaffected population.
The patient is Jack Osbourne (son of Ozzy) who was diagnosed with multiple sclerosis at age 26. His presenting symptom was the episode of vision loss and continues to have numbness, tremors, fatigue and dizziness.
Primary-Progressive
This type of multiple sclerosis (MS) is not very common, occurring in about 10% of people with MS. Primary-progressive multiple sclerosis is characterized by slowly worsening symptoms from the beginning, with no relapses or remissions.
Malignant
Malignant multiple sclerosis is disease with a rapid progressive course, leading to significant disability in multiple neurologicsystems or death in a relatively short time after disease onset.
Secondary-Progressive
In secondary-progressive multiple sclerosis (SPMS) , symptoms worsen more steadily over time, with or without the occurrence of relapses and remissions. Most people who are diagnosed with relapsing-remitting multiple sclerosis will transition to SPMS at some point.
Question 6.
A 30-year old male comes to the office because of progressive dyspnea, chest pain, and cough for 12 months. He states that he initially noticed he was breathless running around after his daughter. He feels that he has also been much more tired than usual over the past 6 months. His temperature is 36.4ºC (97.5ºF), pulse is 80/min, respirations are 18/min, and blood pressure is 118/62 mm Hg. Pulmonary auscultation shows widespread, fine, inspiratory crackles. Spirometry is obtained which shows reduced forced vital capacity (FVC), however his forced expiratory volume in 1 second (FEV1)/FVC ratio is normal. A chest X-ray is also obtained. Which of the following is the most likely diagnosis?
Pneumonia
Pneumonia would not cause the distribution of opacities seen on the chest X-ray. In pneumonia opacities are concentrated to specific regions of infection, and patients are generally febrile.
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease causes obstructive respiratory disease, and therefore would produce a normal forced vital capacity (FVC), but a reduced forced expiratory volume in 1 second (FEV1)/FVC ratio on spirometry.
Pulmonary fibrosis
Major takeaway
Pulmonary fibrosis is an over-deposition of collagen within the interstitium of the lung. This results in reduced forced vital capacity and widespread opacities which can be observed on a chest x-ray.
Main explanation
The opacities and respiratory measurements suggest that pulmonary fibrosis is the most likely diagnosis. Fibrosis involves the deposition of fibrotic tissue within the lung interstitium, reducing lung compliance and reducing functional lung capacity. However, since there is no airway obstruction within the lung, the reduction in forced expiratory volume in 1 second (FEV1) mirrors the reduction in forced vital capacity, and as such the FEV1/FVC ratio appears normal. Although the onset of the disease can be idiopathic, there are a number of potential causes, including asbestosis, tuberculosis, or scleroderma. The characteristic triad of pulmonary fibrosis is the “3Cs.” These are cough, crackles (widespread, fine, inspiratory), and clubbing (of the digits).
Pneumothorax
Pneumothorax would be visible on chest X-ray as a collapsed region of lung, without the opacities observed on the x-ray above. It is also an acute pathology, so this does not fit with a patient who has 12 months of symptoms.
Primary pulmonary malignancy
Primary pulmonary malignancy is cancer that originates from lung tissue. Pulmonary cancer usually represents a single opacity on chest X-ray, and characteristic symptoms are weight loss, night sweats, and fatigue. Some other cancers, such as testicular cancer, can cause a chest X-ray which appears similar with so-called “cannon-ball metastases.”
Question 7.
A 10-year-old girl comes to the office because she has had trouble concentrating in school this year. Her mother reports that she has not been doing her assignments. She tends to have a difficult time sitting still in class, following instructions, and disrupts the other children. She is not disruptive at home, but she will forget to do chores often according to her mother. Which of the following treatments should be recommended for this child?
Atomoxetin
Atomoxetin is a non-stimulant selective norepinephrine reuptake inhibitor and can be effective in people with attention deficit hyperactive disorder. However, due to its side effect profile, it is generally not used as first-line therapy.
Clonidine
Clonidine has been found to be effective in reducing symptoms in ADHD, but it is not as effect as stimulants. Therefore, it is not considered first-line therapy. Clonidine is an alpha-2-adrenergic agonist so it can be useful in over aroused, highly active, or aggressive individuals.
Fluoxetine
Fluoxetine is a selective serotonin reuptake inhibitor that maybe used for depression or as adjunctive therapy for attention deficit hyperactivity disorder (ADHD). Unlike the other therapies described, it does not have an effect on dopamine or norepinephrine. Therefore, it would not be used alone in the treatment of ADHD.
Methylphenidate
Major takeaway
The two major components in the treatment of attention deficit hyperactivity disorder (ADHD) include behavioral and pharmaceutical therapies. Methylphenidate (or Ritalin) is usually the first line stimulant drugs used as medical therapy for this disorder. Cognitive behavioral therapy is used as an adjunctive therapy.
Main explanation
This child has attention deficit hyperactivity disorder (ADHD). The two major components in the treatment of this disorder include behavioral and pharmaceutical therapies. Stimulant drugs are considered the first-line treatment for ADHD in children. These drugs affect the release catecholamines from synapses. It is the increase of norepinephrine and dopamine in the brainstem, midbrain, and frontal cortex that is responsible for the increased attention span and concentration seen in the treatment of these patients.Methylphenidate (or Ritalin) is usually the first line stimulant drugs used as medical therapy for this disorder. Methylphenidateis a psycho-stimulant drug that increases the level of dopamine and norepinephrine by reuptake inhibition.
Parental counseling
Parental counseling may be beneficial in certain situations, but it is not first line therapy. Methylphenidate and individual psychotherapy with a focus on behavior modification would generally be attempted first. Parental counseling can be important in the treatment of oppositional defiant disorder.
Question 8.
A 28-year-old man comes to the physician’s office because of decreased urinary output, and general malaise for 1 week. Examination shows a blood pressure of 190/94 mm Hg. There is also peripheral edema, and mild bilateral flank pain. Urinalysisshows proteinuria, hematuria, and red blood cell casts. A renal biopsy is performed, with nearly all glomeruli appearing as shown. Which of the following is the most likely pathological diagnosis, and what is the most likely prognosis?
Goodpasture disease; disease is self-limited
Goodpasture disease does cause glomerulonephritis, however it also requires pulmonary symptoms such as cough, shortness of breath, and hemoptysis to make a diagnosis. Without treatment patients suffer either advanced kidney failure or lung hemorrhages.
Post-streptococcal glomerulonephritis; disease is self-limited
Post-streptococcal glomerulonephritis classically presents with ‘Coca-Cola’ colored urine and occurs 2 weeks after an upper respiratory infection with Streptococcus pyogenes. Biopsy shows a uniform filling of glomerular capillaries with white blood cells and most cases fully recover.
Post-streptococcal glomerulonephritis; renal failure is imminent
Post-streptococcal glomerulonephritis classically presents with ‘Coca-Cola’ colored urine and occurs 2 weeks after an upper respiratory infection with Streptococcus pyogenes. Biopsy shows a uniform filling of glomerular capillaries with white blood cells and most cases fully recover.
Rapidly progressive glomerulonephritis; disease is self-limited
The renal biopsy shows a cresenteric glomerulus with compressed capillaries. This is characteristic of rapidly progressive (crescentic) glomerulonephritis which rapidly progresses to renal failure.
Rapidly progressive glomerulonephritis; renal failure is imminent
Major takeaway
Rapidly progressive glomerulonephritis (RPGN) is a syndrome of the kidney that is characterized by a rapid loss of renal function with glomerular crescent formation seen in at least 50% of glomeruli on kidney biopsy.
Main explanation
This patient has rapidly progressive glomerulonephritis (RPGN), diagnosed by renal biopsy. RPGN is characterized by a rapid loss of renal function with glomerular crescent formation seen in at least 50% of glomeruli on kidney biopsy.
RPGN is classified pathologically into three categories:
(1) Anti-GBM antibody disease (e.g. Goodpasture syndrome, approximately 3% of cases)
(2) Immune complex disease (e.g. Systemic lupus erythematous (SLE), 45% of cases)
(3) Pauci-immune disease (e.g. Granulomatosis with polyangiitis, 50% of cases). Pauci-immune, also known as negative immunofluorescence, is a general term used to refer to a form of vasculitis that is associated with minimal evidence of hypersensitivity upon immunofluorescence. These diseases are associated with anti-neutrophil cytoplasmic antibodies (ANCA) in about 80% of cases.
While these causes can be detected with serum antibody testing, because the sensitivity and specificity of ANCA testing for pauci-immune glomerulonephritis is only 80-90%, a renal biopsy is recommended. This helps to establish a definite diagnosis and to determine the severity of the disease, which roughly correlates with the number of cresenteric glomeruli seen on biopsy.
The initiation of therapy should not be delayed for biopsy results to be obtained however. If left untreated, RPGN progresses into acute renal failure and death within months.
Question 9.
A 38-year-old woman, gravida 5, para 4, at 30 weeks gestation comes to the office because she is concerned about some vaginal bleeding she had recently. She states that yesterday she noticed that she had blood in her underwear when she went to the bathroom. She describes the flow as less than a period but enough that she needed to use a sanitary pad. She noted that it stopped spontaneously a few hours later. She denies any pain or contractions. Medical history shows that she has not experienced any similar symptoms with her previous pregnancies. Which of the following is the most likely diagnosis?
Ectopic pregnancy
Ectopic pregnancy occurs when the embryo implants outside the uterus, most commonly in the fallopian tubes. It presents with abdominal pain and vaginal bleeding early in pregnancy.
Placenta accreta
Placenta accreta is due to defective implantation of the placenta leading to massive hemorrhage at delivery. Risk factors include prior uterine surgery, including prior cesarean section.
Placenta previa
Major takeaway
Placenta previa is painless vaginal bleeding associated with the implantation of the placentaon or near the internal cervical os.
Main explanation
Placenta previa occurs when the placenta attaches to the lower uterine segment either on or near the cervical os and presents with painless vaginal bleeding. To prevent causing acute hemorrhage, ultrasound localization of the placenta must be done before performing a manual pelvic examination. If the patient is not acutely bleeding, management can be done conservatively as an outpatient. The bleeding is thought to occur when physical changes to the lower portion of the uterus and cervix create shearing forces between the uterus and placenta, thus resulting in a partial detachment of the placenta. This detachment is not nearly as clinically significant as one associated with placental abruption. In fact, one may consider the bleeding to be beneficial in a way, as it is often an early alert that the fetus will need to be delivered via cesarean section rather than a normal vaginal birth.
Placental abruption
Placental abruption is painful vaginal bleeding during the third trimester that is caused by premature detachment of the placentafrom the uterine wall. Risk factors include hypertension and cigarette smoking.
Preterm labor
Because her bleeding spontaneously stopped a day ago, and was not associated with contractions, it is highly unlikely that she is in preterm labor.
Question 10.
A 2-year-old girl comes to the emergency department because of vomiting. The vomiting has been ongoing for the past 3 days but has been getting progressively worse. Today, she had convulsive movements of her entire body. She undergoes head computed tomography which shows a cystic dilation of the fourth ventricle, a partial absence of the cerebellar vermis, and an enlarged posterior fossa. Which of the following is the most likely diagnosis?
Anencephaly
Anencephaly is a forebrain anomaly resulting from the malformation of the anterior neural tube. Anencephaly is associated with a “frog-like appearance” due to the lack of forebrain and open calvarium. Anencephaly is associated with maternal type 1 diabetesand maternal folate supplements can help reduce the risk of the anomaly.
Arnold-Chiari type 1 Malformation
A Chiari malformation is not characterized by an enlarged posterior fossa. Instead, it is characterized by an inferior displacement of the cerebellar tonsils through the foramen magnum. This is often asymptomatic but can have headaches, neck pain, or unsteady gait.
Arnold-Chiari type 2 Malformation
Arnold-Chiari type 2 malformation is characterized by an inferior displacement of the cerebellar tonsils and is more severe than a type 1 malformation. It is associated with myelomeningocele, which could cause paralysis below the defect. The cerebellar tonsillar herniation through the foramen magnum can obstruct CSF flow and cause hydrocephalus.
Dandy-Walker Syndrome
Major takeaway
Dandy-Walker syndrome is characterized by agenesis of the cerebellar vermis and enlargement of the fourth ventricle. This can present with increased intracranial pressure, cerebellar dysfunction, delay of motor development, or signs of hydrocephalus such as progressive enlargement of the skull.
Main explanation
Dandy-Walker malformation is characterized by partial or complete agenesis of the cerebellar vermis, enlargement of the fourth ventricle, cystic formation at the internal base of the skull, and an enlarged posterior fossa. All of these findings fit together, because the cystic dilation of the fourth ventricle will fill the enlarged posterior fossa. Dandy-Walker is also associated with hydrocephalus and spina bifida occulta. Patients with Dandy-Walker syndrome can have delay of motor development and progressive enlargement of the skull. They can also have signs of increased intracranial pressure, such as irritability, vomiting, and convulsions, or cerebellar signs, such as ataxia or discoordination.
Holoprosencephaly
Holoprosencephaly is a forebrain anomaly resulting from a failure of the left and right hemispheres to separate correctly. It can range from cleft lip or palate to cyclopia. Holoprosecephaly is associated with trisomy 13, or Patau syndrome. Mutations in the Sonic Hedgehog signaling pathway is connected to holoprosencephaly.
