UWSA1-1 Flashcards
What is this?
Diabetic nephropathy
When the glomerular sclerosis is nodular, it is described as a Kimmelstiel-Wilson (KW) lesion and is pathognomonic for DN. KW lesions consist of dense hyaline deposits and commonly arise from the glomerular arterioles. As the disease progresses, increased mesangial matrix proteins can lead to global glomerulosclerosis.
Diabetic glomerulosclerosis
pathophys
Diabetic nephropathy (DN) is a common complication of both type 1 and type 2 diabetes mellitus. Prolonged hyperglycemia in diabetes results in glycosylation of endothelial proteins, inflammation, and increased production of growth factors, collagen, and fibronectin. Over time, this results in mesangial expansion, glomerular basement membrane thickening, and glomerular sclerosis.
The first clinical sign of DN is albuminuria, which can progress to overt nephrotic syndrome (eg, peripheral edema, heavy proteinuria, fatty casts) and renal failure. The urine sediment is typically bland (ie, no red or white blood cells or casts).
Focal Segmental Glomerulosclerosis Histology
Focal segmental glomerulosclerosis causes nephrotic syndrome and is associated with foci of sclerosis and hyalinosis in some, but not all, glomeruli.
IgA Nephropathy Presenting symptoms
IgA nephropathy presents with recurrent hematuria associated with upper respiratory infections (synpharyngitic hematuria).
IgA Nephropathy Histology
Light microscopy demonstrates mesangial proliferation, and immunofluorescence demonstrates mesangial immune deposits composed of IgA.
Minimal Change Disease Presenting Features
Minimal change disease causes nephrotic syndrome and typically occurs in children.
Minimal Change Disease Histology
Light microscopy demonstrates normal glomeruli, but electron microscopy demonstrates diffuse effacement of podocytes.
Rapidly Progressive glomerulonephritis presenting features
Rapidly progressive glomerulonephritis causes nephritic syndrome and can occur as an end stage in multiple diseases (eg, Goodpasture syndrome, systemic lupus erythematosus).
Rapidly progressive Glomerulnephiritis Histology
light microscopy demonstrates glomerular crescents composed of proliferating parietal and inflammatory cells.
Cardiac Conduction Velocity Fastest to slowest
Paget Disease Pathophysiology
- Osteoclast dysfunction
- Excessive & disordered bone formation
Paget disease begins with the lytic phase, in which normal bone is resorbed by osteoclasts that are more numerous, are larger, and have many more nuclei (up to 100) than normal osteoclasts (5-10 nuclei). Bone turnover rates increase to as much as 20 times normal.
The second phase, the mixed phase, is characterized by rapid increases in bone formation from numerous osteoblasts. Although increased in number, the osteoblasts remain morphologically normal. The newly made bone is abnormal, however, with collagen fibers deposited in a haphazard fashion rather than linearly, as with normal bone formation. As the osteoclastic and osteoblastic activities of bone destruction and formation repeat, a high degree of bone turnover occurs.
In the final phase of Paget disease, the sclerotic phase, bone formation dominates and the bone that is formed has a disorganized pattern (woven bone) and is weaker than normal adult bone. This woven bone pattern allows the bone marrow to be infiltrated by excessive fibrous connective tissue and blood vessels, leading to a hypervascular bone state.
Paget Disease Clinical manifestations
- Often asymptomatic
- Bone pain & deformity
- Skull: headache, dizziness, hearing loss
- Spine: spinal stenosis, radiculopathy
- Long bones: bowing, focal enlargement, arthritis of adjacent joints
- Elevation in alkaline phosphatase
- X-ray: lytic or mixed lytic/sclerotic lesions; cortical & trabecular thickening
Paget disease of bone is characterized by excessive and disordered bone formation. It commonly involves the skull (eg, headache), spine (eg, radiculopathy, spinal stenosis), or long bones (eg, bone pain, bowing, arthritis of adjacent joints). Long-term complications of Paget disease include fracture, hearing loss, and malignant transformation leading to osteosarcoma.
Paget Disease Complications
- Fracture
- Excessive blood flow: high-output heart failure, vascular steal
- Malignant transformation (eg, osteosarcoma)
Cardiac stress test
coronary steal syndrome
Paget Disease AKA
Osteitis Deformans
Radiologic findings of Osteosacrcoma
Radiographic findings of osteosarcoma include destruction of the normal trabecular bone pattern, mixed radiodense (sclerotic) and radiolucent (lytic) areas, and periosteal new bone formation with lifting of the periosteum (Codman triangle). Adjacent soft tissue often demonstrates ossification in a “sunburst” pattern.
Avascular necrosis caused by
Avascular necrosis can be caused by long-term glucocorticoid use, autoimmune disorders (eg, systemic lupus erythematosus), or conditions that affect blood viscosity (eg, sickle cell disease).
Avascular necrosis radiologic findings
Radiographic findings include the pathognomonic crescent sign, which indicates subchondral collapse at the femoral head
Osteoarthritis ragiographic findings
Osteophytes and joint-space narrowing
Osteoporosis Causes
Osteoporosis is common in older adults, and the risk is increased in patients with corticosteroid exposure (including inhaled corticosteroids)
Osteoporosis radiographic findings
X-ray would show trabecular thinning and possible fracture, rather than lytic/sclerotic lesions and new bone formation.
Secondary Hyperparathyroidism in CKD mechanism
Hypocalcemia and hyperphosphatemia in chronic kidney disease stimulate parathyroid hormone production (secondary hyperparathyroidism).
The resulting effects on bone, known as renal osteodystrophy, can include osteomalacia, osteitis fibrosa cystica, and adynamic bone disease. Patients usually have a known history of advanced renal disease.
Risendronic acid AKA
Risendronate
Risendronate indications
- help prevent osteoporosis
- treat Pagets disease of the bone
Risendronate MOA
Risedronate is a pyridine-based bisphosphonate that inhibits bone resorption caused by osteoclasts
Globus Sensation Description
Globus sensation is the feeling of a “lump in the throat” without accompanying physical, endoscopic, or radiologic findings of esophageal obstruction.
Globus sensation (also called globus hystericus and globus pharyngeus) is a common abnormal sensation of a foreign body, tightness, or fullness in the throat. It is often worse when swallowing saliva and may be alleviated with food or liquid. Globus is a functional disorder of the esophagus and by definition is not due to a structural abnormality or motility disorder. It is frequently associated with anxiety or other underlying psychological distress, but it also happens commonly in patients with no ongoing emotional symptoms.
Most individuals experience the globus sensation intermittently, although it can be persistent. Significant pain, dysphagia, vocal abnormalities, or systemic symptoms (eg, weight loss) are not typical for globus and suggest another condition.
Esophageal Webs Description
Esophageal webs are fragile mucosal folds that cause solid food dysphagia, usually in the mid to lower esophagus. They are most commonly seen in iron deficiency (Plummer-Vinson syndrome) and typically may be seen on barium swallow.
Pseudobulbar Palsy Description
Pseudobulbar palsy is caused by neurologic conditions such as multiple sclerosis and is characterized by dysarthria, dysphagia, dysphonia, and impaired movement of the tongue and facial muscles.
Substernal Goiter description
Substernal goiter occurs when one or both thyroid lobes grow into the thoracic cavity inlet. Most patients are asymptomatic, although rapid enlargement may compress the airway and lead to dyspnea, wheezing, or cough. Swallowing symptoms are less common due to the more posterior location of the esophagus.
Zenker Diverticula Description
Zenker diverticula are mucosal outpouchings caused by motor abnormalities of the esophagus (cricopharyngeus muscle Killians Triangle). They cause dysphagia, regurgitation, aspiration, and halitosis, and are typically diagnosed on barium swallow.
Synovial Fluid aspiration showing
Synovial fluid analysis will typically show numerous neutrophils with slender, needle-shaped monosodium urate crystals. The crystals are negatively birefringent (on polarized light microscopy: yellow when aligned parallel to slow ray and blue when aligned perpendicular).
Gout Synovial Fluid Aspiration
Synovial fluid analysis will typically show numerous neutrophils with slender, needle-shaped monosodium urate crystals. The crystals are negatively birefringent (on polarized light microscopy: yellow when aligned parallel to slow ray and blue when aligned perpendicular).
Gout Description
acute inflammatory monoarthritis, neutrophilic effusion, and numerous needle-shaped crystals has acute gout. Gout is a common disorder of uric acid metabolism characterized by episodic inflammatory arthritis; joint destruction can occur if the disease is left untreated
Gout Cause
Gouty arthritis is caused by precipitation of urate crystals in joints and is most common when uric acid levels are elevated or fluctuating (eg, initiation of diuretic therapy). Normally, the urate crystals have a protective coating of apolipoprotein E or B. When uric acid levels fluctuate or microtrauma occurs, bare urate crystals are shed and exposed to IgG antibodies. The subsequent antibody binding leads to neutrophil phagocytosis and release of inflammatory cytokines (primarily IL-1). This leads to infiltration by neutrophils and macrophages and subsequent inflammatory changes.
Characteristics of an osteoarthritic joint
Characteristic features of an osteoarthritic joint include degeneration of the articular cartilage, narrowing of the joint space, and bony outgrowths (osteophytes) at the articular margins.
Rheumatoid arthritis characterized by
Rheumatoid arthritis is characterized by immune-complex deposition, neutrophil accumulation in the synovial fluid, and perivascular inflammation of the synovial stroma. Synovial pannus formation
Acute septic arthritis synovial fluid features
Acute septic arthritis frequently affects the knee and may produce a neutrophilic effusion. However, synovial fluid would show microorganisms rather than numerous crystals.
Traumatic Joint Effusion Synovial fluid
Effusion in acute traumatic joint injury would usually be serosanguineous or frankly bloody. Crystals are not typically present in the joint fluid.
What is this?
- Endometrial glands within an endometrioma continue to proliferate and shed in response to pulsatile estrogen and progesterone. This cyclic shedding without an outlet can cause dysmenorrhea despite regular menses (eg, every 29 days). Over time, the shed cells and by-products of hemoglobin breakdown (eg, hemosiderin) can cause intraperitoneal inflammation, tissue fibrosis, and pelvic adhesions (eg, ovary adhered to the pelvic sidewall).
- Inflammation also recruits macrophages, which ingest the blood by-products and appear as pigmented, hemosiderin-laden macrophages.
Endometriosis Description
- An adherent adnexal mass and severe abdominal pain with menses (ie, dysmenorrhea) are most consistent with endometriosis. Endometriosis is characterized by the presence of endometrial glands and stroma in an extrauterine location, likely from a combination of cellular metaplasia and retrograde menstruation. The most common site for ectopic endometrial implants is the ovary; these implants can form a cystic ovarian mass that is composed of endometrial tissue and old blood (ie, an endometrioma).
- Endometrial glands within an endometrioma continue to proliferate and shed in response to pulsatile estrogen and progesterone. This cyclic shedding without an outlet can cause dysmenorrhea despite regular menses (eg, every 29 days). Over time, the shed cells and by-products of hemoglobin breakdown (eg, hemosiderin) can cause intraperitoneal inflammation, tissue fibrosis, and pelvic adhesions (eg, ovary adhered to the pelvic sidewall). Inflammation also recruits macrophages, which ingest the blood by-products and appear as pigmented, hemosiderin-laden macrophages.
Epithelial Ovarian Cancer possible presentation
Epithelial ovarian cancer can present as an adherent ovarian mass. However, microscopy typically reveals stromal invasion by atypical epithelial cells with enlarged nuclei. These tumors do not present with dysmenorrhea.
Granulosa-cell tumors histological features
- Granulosa cell tumors are sex cord stromal tumors; histologic findings include Call-Exner bodies, which are clusters of atypical granulosa cells that have scant cytoplasm and “coffee-bean” nuclei.
granulosa cell tumors menses
In addition, unlike endometriosis, those with granulosa cell tumors typically have irregular menses due to tumor secretion of estrogen and inhibin.
Mature cystic teratomas description
(ie, dermoid cysts) are benign ovarian germ cell tumors that can contain mesodermal, endodermal, and/or ectodermal tissue (eg, squamous epithelium, sebaceous glands).
Mature cystic teratomas menses
cysts are not typically associated with dysmenorrhea.
Mature Cystic Teratomas histology
Sertoli-Leydig cell tumors histology
Sertoli-Leydig cell tumors are rare sex cord stromal tumors composed of tubules of Sertoli cells alongside eosinophilic Leydig cells with prominent nucle
Sertoli-Leydig Cell tumors menses
These tumors secrete testosterone; therefore, patients typically have signs of virilization (eg, voice deepening, clitoromegaly) and irregular menses.
Sertoli-Leydig cell tumors secrete
Testosterone (androgens)
Teratogenic effects of ACE inhibitors and ARBs
Results in renal hypoplasia and dysplasia
↓
↓ fetal urine production
↓
Fetal compression
Mechanism of teratogenicity of ACE inhibitors and ARBs
ACE inhibitors and ARBs are highly teratogenic and contraindicated in pregnancy. Both medications decrease the activity of angiotensin II, which is critical for normal renal development and fetal urine production. ACE inhibitors prevent the conversion of angiotensin I to II, and ARBs block angiotensin II activity at the angiotensin II receptor type 1 (AT1). Use of either medication during pregnancy can cause fetal renal hypoplasia or dysgenesis and decreased fetal urine output.
Because fetal urine is the main component of amniotic fluid, fetal renal hypoplasia typically equates to low amniotic fluid levels (ie, oligohydramnios). Amniotic fluid is vital for fetal lung development, and normal levels typically protect against fetal compression; in contrast, chronically low levels can lead to pulmonary hypoplasia and limb compression or deformity (ie, Potter sequence). Low amniotic fluid levels also correspond with low fundal height and restriction of fetal movement that can contribute to severe fetal growth restriction.
Potter sequence pathophys
- Urinary tract abnormailty
- leads to oligohydramnios and sequence
Congenital CMV features
Congenital cytomegalovirus infection can cause fetal growth restriction, it is associated with microcephaly and periventricular intracranial calcifications
Fetal Posterior Urethral valves
- Fetal posterior urethral valves, membranes that obstruct the urethra, can cause decreased fetal urine output and resultant oligohydramnios. However, the backup of urine typically causes bilateral hydronephrosis (ie, large kidneys)
Importance of folic acid supplementation during pregnancy
Folic acid supplementation is recommended during pregnancy. Inadequate maternal folate levels can increase the risk for neural tube defects (eg, anencephaly, myelomeningocele)
Lead to polyhydramnios from neural tube defects and neuromuscular defects preventing adequate swallowing,
Fetal Alcohol Syndrome
Maternal alcohol use is teratogenic (ie, fetal alcohol syndrome) and may cause fetal growth restriction. However, it is not associated with abnormal fetal kidney development. Fetal ultrasound findings can include microcephaly and facial dysmorphia (eg, micrognathia)
Viral replication cycle and anti-viral therapy
Oseltamivir MOA
- Oseltamivir (Tamiflu) is a sialic acid analogue that inhibits the neuraminidases of the influenza A and influenza B viruses.
- Newly formed virus particles initially remain attached to cells and respiratory tract mucins through hemagglutinin binding of glycoconjugate receptors.
- Neuraminidase cleaves the terminal sialic acid residues on these receptors, allowing for the release of attached virions from infected cells and subsequent viral spread.
- Neuraminidase inhibitors force the newly synthesized virions to remain adherent to the host cell surface, ultimately forming viral aggregates that are unable to infect new host cells.
- Through this mechanism of action, oseltamivir can shorten the course of influenza A and B infections when taken within 48 hours of symptom onset.
Oseltamivir Clinical use
Influenza A or B
Penicillin MOA
penicillins, which interact with transpeptidase (penicillin-binding protein), inhibit peptidoglycan cell wall synthesis
Fluoroquinolones MOA
Fluoroquinolones inhibit DNA gyrase and topoisomerase, which participates in supercoiling.
Aminoglycosides MOA
Aminoglycosides bind to bacterial ribosomes, inhibiting protein synthesis primarily by binding to the aminoacyl site of 16S ribosomal RNA within the 30S ribosomal subunit
Amantadine MOA
- Amantadine prevents viral assembly and also inhibits viral release through interactions with the viral M2 protein.
- Amantadine is no longer used due to resistance.
Ribavirin MOA
- Ribavirin inhibits viral RNA polymerase activity and RNA fragment initiation and elongation, leading to viral protein synthesis inhibition.
- It is used in chronic hepatitis C infection and in some cases of respiratory syncytial virus infection.
Ribavirin Clinical use
It is used in chronic hepatitis C infection and in some cases of respiratory syncytial virus infection.
Trypsinogen activation
Trypsinogen: Enterokinase in the duodenal brush border cleaves this pancreatic protease, activating it to trypsin. Trypsin then cleaves and activates other pancreatic proenzymes such as proelastase and procarboxypeptidase.
DNA laddering description
The appearance of DNA fragments in multiples of 180 base pairs on gel electrophoresis is known as DNA laddering. This finding is a sensitive indicator of apoptosis, a process of programmed cell death that can occur when regulating factors (eg, interleukins) are withdrawn from proliferating cells. Laddering arises from the action of specific endonucleases during karyorrhexis. These endonucleases cleave DNA at internucleosomal linker regions, which occur at 180-base pair intervals in the genome.
A hallmark feature of some cancer cells is their ability to evade programmed cell death, particularly the intrinsic (mitochondrial) pathway of apoptosis.
Follicular B-cell lymphoma pathogenesis
The appearance of DNA fragments in multiples of 180 base pairs on gel electrophoresis is known as DNA laddering. This finding is a sensitive indicator of apoptosis, a process of programmed cell death that can occur when regulating factors (eg, interleukins) are withdrawn from proliferating cells. Laddering arises from the action of specific endonucleases during karyorrhexis. These endonucleases cleave DNA at internucleosomal linker regions, which occur at 180-base pair intervals in the genome.
A hallmark feature of cancer cells is their ability to evade programmed cell death, particularly the intrinsic (mitochondrial) pathway of apoptosis. A well-established mechanism by which malignant lymphoid cells avoid apoptosis is via overexpression of BCL2, an antiapoptotic protein. In fact, most follicular B cell lymphomas are associated with a t(14;18) translocation that leads to BCL2 overexpression.
Follicular B-cell lymphoma genetics
- most follicular B cell lymphomas are associated with a t(14;18) translocation that leads to BCL2 overexpression and apoptosis evasion
- BCL2 is an antiapoptotic protein of the mitochronidal (intrinsic pathway).
Warburg Effect
Malignant cells can undergo high rates of glycolysis to produce the macromolecules necessary to sustain rapid cellular growth (Warburg effect).
Bronchial parasympathetic control
Acetylcholine stimulates muscarinic M3 receptors on bronchial smooth muscle, activating the Gq-phospholipase C-IP3 pathway, which increases intracellular calcium and triggers muscle contraction (bronchoconstriction)
Examples of inhaled antimuscarinics
- Ipratropium
- Tiotropium
Inhaled muscarinic agonist
Methacholine is an inhaled muscarinic agonist that can help diagnose asthma as it promotes bronchoconstriction (methacholine challenge).
Methacholine challenge
- Cholinergic agents activate muscarinic receptors on bronchial smooth muscle, leading to increased muscle contraction intensity (bronchoconstriction).
- Methacholine is an inhaled muscarinic agonist that can help diagnose asthma as it promotes bronchoconstriction (methacholine challenge).
Edrophonium MOA
Edrophonium is a short-acting acetylcholinesterase inhibitor that can be used to support the diagnosis of myasthenia gravis (Tensilon test).
Phenylephrine MOA
Phenylephrine is a potent alpha-1 receptor agonist that promotes contraction of vascular smooth muscle (vasoconstriction).
Considerations of Benzodiazepine metabolism
- Slower benzodiazepine metabolism and elimination in the elderly increase the likelihood of adverse effects such as confusion, anterograde amnesia, ataxia, and falls
- Benzodiazepines are metabolized in the liver and then excreted in the urine. Most benzodiazepines are metabolized via CYP-mediated hepatic oxidative reduction (phase I) followed by glucuronide conjugation (phase II).
- Elderly individuals have reduced oxidative reduction, resulting in slower elimination of many drugs metabolized by the liver.
- However, certain benzodiazepines (lorazepam, oxazepam, temazepam) undergo only glucuronide conjugation, which tends to be relatively preserved in the elderly and those with liver disease.
- In addition, elderly individuals have an increased volume of distribution of lipid-soluble drugs (decreased total body water and mass; increased body fat) as well as decreased renal function, which also contribute to prolonged elimination time of drugs.
Benzodiazepine in the elderly adverse effects
Slower benzodiazepine metabolism and elimination in the elderly increase the likelihood of adverse effects such as confusion, anterograde amnesia, ataxia, and falls
Benzodiazepine tolerance
Tolerance is associated with the length and extent of benzodiazepine use. Prolonged exposure decreases the GABA receptor’s affinity for the drug, resulting in less GABA activity and the necessity for increased dosages to achieve the same effect
Anticholinergic Toxicity
7 main symptoms
Central nervous involvement causes confusion, visual hallucinations, psychosis, and seizure. Coma and respiratory failure can develop in severe cases.
Jimson Weed
Jimson weed seeds (Datura stramonium). Jimson weed is an easily obtained drug of abuse that contains a number of anticholinergic toxins, including atropine, hyoscyamine, and scopolamine. Toxicity may also be seen with excess intake of pharmacologic anticholinergics, such as antihistamines (eg, hydroxyzine, diphenhydramine), antipsychotics (eg, chlorpromazine, olanzapine), antispasmodics (eg, dicyclomine, hyoscyamine), and cyclic antidepressants (eg, amitriptyline, desipramine).
Cocaine Toxicity
Cocaine toxicity is characterized by increased energy, tachycardia, and hypertension; vasoconstriction can result in myocardial ischemia and chest pain. Although tactile hallucinations of formication (ie, sensation of bugs crawling on skin) can occur, patients with cocaine intoxication are typically diaphoretic
To determine the causal mutation, blood was collected from the affected children, DNA was extracted from peripheral leukocytes, and the fibroblast growth factor receptor (FGFR) gene was analyzed. Both affected offspring were found to be heterozygous for the same mutation in the FGFR gene. Which of the following is the most likely explanation for this unaffected couple having children with the disorder?
Germline mosaicism
Types of mosaicism
- Somatic Mosaicism
- Germline Mosaicism
- Combined Mosaicism
Mosaicism description
- Mosaicism is defined as the presence of multiple, genetically different cell lines within the body. Typically, mosaicism results from a mutation during the first stages of embryonic development. The earlier the mutation occurs, the more daughter cells that are affected.
- Mosaicism can be classified as germline, somatic, or both.
- Germline mosaicism involves only oocytes or spermatocytes and should be considered when a genetic mutation is identified in the offspring but not in the parents.
- The likelihood that future offspring will be affected by the same mutation depends on the proportion of mutant to wild-type germ cells in the mosaic parent. The presence of 2 affected children in a family suggests that the number of mutant germ cells in the mosaic parent is high.
Fish Oil Consumption recommended for
Fish oil supplementation is often recommended for those patients with refractory hypertriglyceridemia
Diabetic patients routine examinations
- Individuals with diabetes mellitus should inspect their feet daily for signs of trauma or infection.
- Neurologic evaluation of Achilles tendon reflex, vibration sense, and pain and temperature sensation should be performed periodically (yearly) on diabetic patients
What is this?
Acute promyelocytic leukemia
Acute Promyelocytic Leukemia Histological Features
Auer rods are azurophilic, needle-shaped cytoplasmic inclusions formed by the fusion of primary granules found in myeloblasts and promyelocytes. The rods can be seen on peripheral blood smears and bone marrow aspirates of patients with acute myeloid leukemia, particularly acute promyelocytic leukemia (APL).
What are Auer Rods
Auer rods are azurophilic, needle-shaped cytoplasmic inclusions formed by the fusion of primary granules found in myeloblasts and promyelocytes. The rods can be seen on peripheral blood smears and bone marrow aspirates of patients with acute myeloid leukemia, particularly acute promyelocytic leukemia (APL).
Acute Promyelocytic Leukemia Genetics
- APL is caused by a t(15;17) chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 and the promyelocytic leukemia gene on chromosome 15. This translocation is highly specific for APL and is not seen in association with other leukemias or solid tumors.
- PML-RARA
Acute Promyelocytic Leukemia Clinical Features
Clinical features of APL include complications of pancytopenia (eg, weakness, fatigue, infections, gingival bleeding, ecchymoses) and disseminated intravascular coagulation.
Treatment with all-trans retinoic acid should be initiated as soon as possible after the diagnosis is suspected due to a high rate of early mortality from associated hemorrhage.
Acute Promyelocytic Leukemia Tx
Treatment with all-trans retinoic acid should be initiated as soon as possible after the diagnosis is suspected due to a high rate of early mortality from associated hemorrhage.
Burkitt Lymphoma Genetics
t(8;14)
MYC on Chromosome 8 is translocated to 14 which disrupts MYCs expression
The reciprocal chromosome translocation, t(8;14), involving the Ig heavy chain locus on chromosome 14 and the c-myc oncogene on chromosome 8
MYC is an oncogene so when overly expressed can lead to uncontrolled cell growth and proliferation
Burkitt Lymphoma Histology
Tumor cells classically have round nuclei with basophilic cytoplasm containing prominent lipid vacuoles.
Chronic Myeloid Leukemia Histology
Peripheral blood smear shows leukocytosis with many mature and immature myeloid cells.
Chronic Myeloid Leukemia mutation
- t(9;22) resulting in BCR-ABL1 fusion gene
- Bcr-Abl induces mitogenesis in fibroblast and hematopoietic cell transformation models and protects cells from apoptosis induced by numerous stimuli including cytokine withdrawal, DNA damage, and Fas activation (2, 3, 12, 24–26)
Acute Lymphoblastic Leukemia Histology
- High nuclear to cytoplasmic ratio and immature chromatin
- Peripheral blood smear typically demonstrates anemia, thrombocytopenia, and lymphoblasts.
Acute Lymphoblastic Leukemia translocation Mutation
- t(12;21) is the most common translocation in childhood B-cell acute lymphoblastic leukemia.
- This translocation fused two genes, tel and AML1
Follicular Lymphoma Histology
The peripheral blood smear will often show malignant cells with notches or clefts (centrocytes).
Follicular Lymphoma Translocation mutation
t(14;18) is common in follicular lymphoma
BCL2 and Ig chain genes
Effects of IL-2
IL-2 exerts strong proinflammatory effects on most lymphocyte-derived cells, as follows:
- CD4 cells: IL-2 acts in an autocrine manner to increase proliferation of activated CD4 lymphocytes and induce differentiation into type 1 and type 2 helper subtypes. These cells then secrete cytokines (eg, interferon gamma, tissue necrosis factor alpha, interleukin-4) that drive the inflammatory response. IL-2 also stimulates the generation of long-lasting memory cells.
- CD8 cells: IL-2 also promotes the clonal expansion of CD8 cells and stimulates activated CD8 cells to increase cytotoxic killing via the release of perforin, granzymes, and proinflammatory cytokines.
- NK cells: IL-2 stimulates the clonal expansion of NK cells and dramatically enhances their cytotoxic killing.
- IL-2 also exerts potent anti-inflammatory effects via stimulation of regulatory T (Treg) cells. Treg cells constitutively express the IL-2 receptor, which allows them to rapidly activate and proliferate in areas of inflammation (where IL-2 levels are high). Treg cells downregulate the immune response via the expression of surface molecules (eg, CTLA-4) and anti-inflammatory cytokines (interleukin-10, TGF-beta). Therefore, they serve as an important counterbalance to runaway immune activation
IL-2 Effects on CD4 cells
CD4 cells: IL-2 acts in an autocrine manner to increase proliferation of activated CD4 lymphocytes and induce differentiation into type 1 and type 2 helper subtypes. These cells then secrete cytokines (eg, interferon gamma, tissue necrosis factor alpha, interleukin-4) that drive the inflammatory response. IL-2 also stimulates the generation of long-lasting memory cells.
IL-2 Effects on CD8 cells
CD8 cells: IL-2 also promotes the clonal expansion of CD8 cells and stimulates activated CD8 cells to increase cytotoxic killing via the release of perforin, granzymes, and proinflammatory cytokines.
IL-2 effects on NK cells
NK cells: IL-2 stimulates the clonal expansion of NK cells and dramatically enhances their cytotoxic killing.
IL-2 effects on T-reg cells
IL-2 also exerts potent anti-inflammatory effects via stimulation of regulatory T (Treg) cells. Treg cells constitutively express the IL-2 receptor, which allows them to rapidly activate and proliferate in areas of inflammation (where IL-2 levels are high). Treg cells downregulate the immune response via the expression of surface molecules (eg, CTLA-4) and anti-inflammatory cytokines (interleukin-10, TGF-beta). Therefore, they serve as an important counterbalance to runaway immune activation
Granulocyte-macrophage colony-stimulating factor is secreted by
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is secreted by endothelial cells, fibroblasts, macrophages, T cells, and NK cells in response to endotoxin or inflammatory cytokines.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) Function
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is secreted by endothelial cells, fibroblasts, macrophages, T cells, and NK cells in response to endotoxin or inflammatory cytokines. It is a potent stimulator of neutrophil production and also promotes the release of neutrophils from the bone marrow.
IFN-α is secreted by
is secreted by a variety of immune (eg, monocytes, macrophages, B cells, NK cells) and nonimmune (eg, endothelial cells, fibroblasts) cells in response to viral infection. It directly inhibits viral replication and activates cells involved in cytotoxic killing (eg, CD8 cells, NK cells).
IFN-α Function
It directly inhibits viral replication and activates cells involved in cytotoxic killing (eg, CD8 cells, NK cells).
IL-1 is secreted by
Interleukin-1 (IL-1) is secreted primarily by macrophages, dendritic cells, monocytes, and fibroblasts.
IL-1 function
IL-1 increases adhesion molecules on endothelial cells, which promotes phagocyte and lymphocyte recruitment; it also triggers significant systemic effects (eg, fever, vasodilation, hyperalgesia).
Cell junctions and Cadherins
What are Cadherins?
- Cadherins are calcium-dependent adhesion molecules that bind epithelial cells together within tissues. Cadherin molecules on epithelial cells bind to cadherin molecules on adjacent cells to form adherens junctions and desmosomes.
- Cadherins (eg, desmogleins, desmocollins, E-cadherin) are adhesion molecules that bind epithelial cells together within tissues. They are transmembrane proteins that interact intracellularly with intermediate proteins (catenin, plakoglobin, desmoplakin), which facilitate binding to intermediate filaments (keratin) or microfilaments (actin) within the cytoplasm.
- Externally, cadherin molecules on epithelial cells bind to cadherin molecules on adjacent cells to form adherens junctions and desmosomes. Interactions between the extracellular domains of adjacent cadherins are calcium-dependent; removing calcium from the extracellular fluid will cause dissociation of cadherin-mediated junctions, leading to loss of cell-cell adhesion.
Fibronectin function
extracellular matrix glycoproteins that bind cell surface integrins, facilitating cell binding to the extracellular matrix
Laminin function
extracellular matrix glycoproteins that bind cell surface integrins, facilitating cell binding to the extracellular matrix
Cell junctions
Hemidesmosomes function
cell adhesion to the basement membrane is mediated primarily by hemidesmosomes. These structures rely on integrins, which are not calcium-dependent, rather than cadherins.
Molluscum contagiosum pathogenesis
Molluscum contagiosum is caused by a poxvirus (MC virus) and is transmitted through direct contact or fomites.
Molluscum contagiosum histology
Microscopy will show epidermal hyperplasia along with molluscum bodies, large eosinophilic cytoplasmic inclusions made of virus particles. Molluscum bodies can also be identified in the material expressed from the umbilicated lesions.
Molluscum contagiosum clinical features
Molluscum contagiosum is characterized by firm, flesh-colored papules on the skin and mucous membranes. The papules are often pruritic and have umbilicated centers containing white, curd-like material. Molluscum contagiosum is caused by a poxvirus (MC virus) and is transmitted through direct contact or fomites. In children, lesions commonly appear on the eyelids, face, or trunk. In adults, sexual transmission may lead to lesions on the trunk and anogenital region. HIV-positive or otherwise immunocompromised individuals may have a prolonged course with widely distributed papules, facial involvement, and lesion counts numbering in the hundreds.
Microscopy will show epidermal hyperplasia along with molluscum bodies, large eosinophilic cytoplasmic inclusions made of virus particles. Molluscum bodies can also be identified in the material expressed from the umbilicated lesions.
Basal cell Carcinoma gross histology
typically forms slow-growing papules, often with ulceration or a rolled border
Basal cell carcinoma Histology
Histopathology shows nests or strands of basaloid cells with hyperchromatic nuclei. The cells at the periphery often display parallel alignment (palisading).
What is this?
Basal Cell Carcinoma
what is this?
Verruca Vulgaris
What is Verruca Vulgaris?
Verruca vulgaris (common warts) due to human papillomavirus causes non-umbilicated, skin-colored or pink papules or growths.
Biopsy is characterized by undulating epidermal hyperplasia with enlarged nuclei and cytoplasmic vacuolization (koilocytosis) forming perinuclear halos.
Verruca Vulgaris Histology
Biopsy is characterized by undulating epidermal hyperplasia with enlarged nuclei and cytoplasmic vacuolization (koilocytosis) forming perinuclear halos.
Cryptococcus Neoformans Histology
- Microscopic assessment will show budding encapsulated yeast
- Thick polysaccharide capsule
- India ink
What stimulates the pancreas to secrete HCO3- rich fluid into the duodenum?
- The delivery of acidic (pH < 4.5) chyme from the stomach to the duodenum triggers gallbladder bile release and stimulates the S cells in the crypts of Lieberkühn to release secretin into systemic circulation.
- The pancreas is then prompted by secretin to generate bicarbonate-rich fluid, which neutralizes the hydrogen ions in chyme. The establishment of a neutral pH in the duodenal lumen prevents injury to the duodenal mucosa and allows digestive enzymes to function properly.
Posterior Knee Dislocation
At risk for popliteal artery injury and tibial nerve
A 37-year-old woman, gravida 2 para 1, comes to the emergency department with lower abdominal pain, fever, and chills on postoperative day 5. The patient underwent an emergency cesarean delivery due to fetal concerns at 39 weeks gestation after 20 hours of labor. She had a normal postpartum course and is breastfeeding her infant. Her prenatal laboratory studies were negative for infection. The patient has a history of chlamydia that was treated with antibiotics 4 years ago. Temperature is 38.9 C (102 F), blood pressure is 110/70 mm Hg, and pulse is 110/min. Physical examination reveals a tender lower abdomen and foul-smelling vaginal discharge. Breast examination is normal. There is no costovertebral tenderness. Laboratory results show leukocytosis with a neutrophilic predominance. Which of the following is the site of infection in this patient?
Uterus (Post-partum endometritis)
Posterior Endometritis pathophysiology
- Postpartum endometritis is a polymicrobial uterine infection (eg, Gardnerella vaginalis, Peptococcus, Bacteroides, Staphylococcus epidermidis, group B Streptococcus) that is especially common after a cesarean delivery.
- The cervix serves as a protective barrier to the normally sterile upper genital tract. With labor and delivery, especially with prolonged labor or rupture of membranes, the uterine cavity becomes increasingly contaminated with cervicovaginal flora. After a cesarean delivery, the presence of foreign bodies (eg, suture material, surgical instruments) and post-surgical collections of blood (eg, hematomas) serve as a nidus for microbiological inoculation. Suture repair of the uterine incision can cause necrosis of the myometrial tissue, which further contributes to inflammation and infection of the uterus.
Postpartum endometritis S&S
- Typical manifestations include fever, lower abdominal pain, and malodorous lochia (eg, vaginal discharge) after delivery.
- Physical findings include uterine (eg, fundal) tenderness and leukocytosis.
- Peritonitis and sepsis can arise with hematogenous spread of pathogens.
Mastitis description
Mastitis is a breast infection during lactation and is caused by Staphylococcus aureus from the infant’s oral flora.
Mastitis S&S
Typical presentation is breast tenderness and erythema with a high fever.
Pelvic Inflammatory Disease Description
- pelvic inflammatory disease (eg, gonorrhea, chlamydia) begins with cervical infection (cervicitis), which, can ascend to the uterus (non-obstetric endometritis) and fallopian tube (salpingitis).
- Hx of chlamydia and gonoirrhea infection is a risk factor PID
Bartholin Cyst
The greater vestibular (Bartholin) glands drain into the Bartholin duct. Blockage of a Bartholin duct leads to mucus accumulation and cyst formation. Infection of the cyst can result in a labial abscess, a painful unilateral labial mass occasionally accompanied by purulent vaginal discharge.
Herpes Zoster Pathophysiology
- herpes zoster (shingles).
- Although most commonly seen in adults age >50, herpes zoster can occur in children, especially those with primary varicella infection (chicken pox) in the first year of life.
- Herpes zoster results from reactivation of latent varicella zoster virus (VZV).
- On resolution of the primary infection, immunity develops and VZV retreats to the dorsal root ganglion of cutaneous sensory nerves, where it remains in a latent state.
- Risk factors for reactivation of latent VZV include age, trauma, malignancy, and immunosuppression.
Shingles S&S
Herpes zoster manifests clinically with a prodrome of neuropathic pain that is typically unilateral and isolated to one dermatome. Crops of grouped vesicles with underlying erythema subsequently erupt in that same dermatome accompanied by severe pain.
What is this?
Atopic Dermatitis
Atopic Dermatitis Pathophysiology
- Affects infants and young children and is frequently associated with a family history of atopy (eg, asthma, food allergies, allergic rhinitis).
- Infants typically experience eruptions on their cheeks and diaper area; flexural surfaces are often involved in older children.
Measels rash features
- is rarely seen in the United States due to current immunization practices.
- The viral exanthem associated with measles begins on the head and face and spreads downward to involve the trunk and lower extremities.
- The pathognomonic lesions are red/blue Koplik spots on the buccal mucosa.
What is Nummular Eczema?
- Nummular eczema most commonly occurs in the setting of xerosis.
- Use of harsh soaps and exposure to environmental irritants can exacerbate the condition.
- Nummular eczema presents with pruritic, coin-shaped, erythematous patches.
Psoriasis rash feautres
- Psoriasis causes well-demarcated, erythematous plaques with overlying silvery scale on the extensor surfaces of the extremities.
- It is more commonly seen in adults and appears to be triggered by environmental factors such as smoking, weather changes, and stress.
Shingles description
- Herpes zoster results from reactivation of latent varicella zoster virus in the dorsal root ganglion.
- It presents as an eruption of vesicles with surrounding erythema isolated to a single dermatome accompanied by severe neuropathic pain.
- It can be seen at any age after initial varicella infection, although adults age >50 are at greatest risk.
Acting out description
Expressing unacceptable feelings through actions
Denial Description
Behaving as if an aspect of reality does not exist
Displacement Description
Transferring feelings to less threatening object/person
Intellectualization Description
Focusing on nonemotional aspects to avoid distressing feelings
Passive aggression description
Avoiding conflict by expressing hostility covertly
Projection Description
Attributing one’s own feelings to others
Rationalization Description
Justifying behavior to avoid difficult truths
Reaction formation Description
Transforming unacceptable feelings/impulses into the opposite
Regression Description
Reverting to earlier developmental stage
Splitting Description
Experiencing a person/situation as either all positive or all negative
Mature Defence Mechanisms
2 listed
- Sublimation
- Suppression
Sublimation Description
Channeling impulses into socially acceptable behaviors
Suppression Description
Putting unwanted feelings aside to cope with reality
Receptor vs non-receptor Tyrosine Kinases
- These receptors are transmembrane proteins that have a ligand-binding extracellular region, a hydrophobic transmembrane region, and an intracellular (cytoplasmic) domain with inducible tyrosine kinase activity.
- Ligand binding to the extracellular portion of a tyrosine kinase receptor causes dimerization of 2 identical receptor subunits.
- Each subunit phosphorylates the other, causing a conformational change in the intracellular domains of the tyrosine kinase receptor dimer.
- This conformational change exposes each subunit’s catalytic domain, and phosphorylation of tyrosine residues on target proteins ensues.
- The difference comes in whether the receptor has intrinsic tyrosine kinase activity or if there is a cytoplasmic tyrosine kinase that binds to and dimerizes receptor to continue downstream signalling
PLC-IP3 Pathway
Receptor Mediated Endocytosis
Receptor-mediated endocytosis involves pooling of receptors in clathrin-coated regions, or “pits,” in the cell membrane.
When ligand binds to these receptors, a signal is transduced that results in internalization of the ligand-receptor complex into a vesicle.
The LDL receptor functions in this manner.
Features of Intranasal Cocaine Use
- headaches, chronic nasal discharge, atrophic nasal mucosa, and perforation of the nasal septum likely has cocaine use disorder, including intranasal cocaine use.
- Respiratory tract findings associated with intranasal cocaine use include oropharyngeal ulcers, ulceration or perforation of the palate, and osteolytic sinusitis.
- Clinical features of intrnasal cocaine use may mimic granulomatosis with polyangiitis (previously Wegener granulomatosis) and may even be associated with a positive titer for antineutrophil cytoplasmic antibody. The effects of cocaine on the nasal mucosa are mediated in large part by local vasoconstriction with tissue ischemia. However, other factors, including impaired cell-mediated immunity and reduced mucociliary clearance, also play a role, as would the effects of any impurities in the inhaled substance.
Features of Allergic Rhinitis
Allergic rhinitis causes sneezing, rhinorrhea, nasal congestion, and pruritus of the eyes, nose, and palate. The mucosa would usually be thickened, often with mucosal polyps.
Aspirin Intolerance features
Aspirin intolerance is characterized by asthma, nasal polyps, and aspirin sensitivity.
What is Rhinitis medicamentosum?
Rhinitis medicamentosum refers to chronic nasal congestion in patients who have become habituated to nasal decongestant sprays
What is Nasal vestibulitis?
Nasal vestibulitis is a staphylococcal infection of the internal nares and associated hair follicles. It can cause mucosal edema and nasal congestion, but the septum is not affected.
A 32-year-old male sustains a knife injury to his back and undergoes a right nephrectomy. His past medical history is insignificant. Which of the following best describes his glomerular filtration rate (GFR) compared to baseline?
immediately After Surgery: 50%
Six weeks after surgery: 80%
Although heminephrectomy causes an acute reduction of the total GFR by 50%, the nephrons in the remaining kidney undergo significant hemodynamic and structural adaptations to allow for the single nephron GFR (SNGFR) to rise. The end result is a long-term reduction of total GFR to approximately 80% of the baseline value. Within one week of nephrectomy in a kidney donor, the GFR in the remaining kidney has already increased to 65-70% of the previous two-kidney value, approaching 80% by four to six weeks post-nephrectomy.
Identify
Sildenafil MOA
selective phosphodiesterase-5 inhibitor (eg, sildenafil)
prevents breakdown of cGMP which leads to increased relaxation
How does Sildenafil help with Erectile Dysfunction
The photomicrograph above depicts a hematoxylin- and eosin-stained transverse section of the penis.
selective phosphodiesterase-5 inhibitor (eg, sildenafil). Local release of nitric oxide during sexual stimulation increases the activity of soluble guanylate cyclase in smooth muscle cells.
Simultaneous inhibition of phosphodiesterase-5 further augments intracellular cyclic guanosine monophosphate (cGMP) concentrations.
cGMP mediates relaxation in the smooth muscle cells that surround the cavernous venous sinuses of the corpora cavernosa (area B).
Through this mechanism, phosphodiesterase-5 inhibitors facilitate vascular congestion, causing the corpora to become engorged and sustaining the erection.
Corpus Spongiosum function
Maintains patency of urethra
Visual Pathways
Right Anopia
No vision in right eye
Sever right optic nerve
Bitemporal hemianopia
Sever optic chaisma
no lateral visual fields
Binasal Hemianopia
No vision in medial fields
Sever optic tract lateral to optic chaisma
Left homonymous hemianopia
No Left sided vision
Sever right optic tract proximal to optic chaisma
Left homonymous inferio quadrantanopia
left pie on the floor
sever right dorsal optic radiation
Left homonymous superio quadrantanopia
Left Pie in the sky
Sever right meyer loop
Anterior pituitary embryonic origin
During embryonic development, the anterior pituitary (adenohypophysis) is formed from an ectodermal diverticulum arising from the oral cavity known as Rathke’s pouch.
Craniopharyngiopharyngiomas
Craniopharyngiomas are slow-growing suprasellar tumors arising from remnants of Rathke’s pouch. They have a bimodal age distribution with one peak in childhood and another peak in adults (age 50-75).
Individuals typically present insidiously with headaches, signs of pituitary dysfunction (eg, growth failure in children), and visual disturbances. Bitemporal hemianopia often occurs due to tumor compression on the central portion of the optic chiasm.
Neuroimaging classically reveals a calcified mass in the suprasellar region.
Craniopharyngiomas radiographic findings
Neuroimaging classically reveals a calcified mass in the suprasellar region.
A 48-year-old woman is hospitalized for lobar pneumonia. Blood and sputum cultures are obtained, and she is started on appropriate antibiotic therapy. After 3 days of treatment, the patient continues to have persistent fever and chills. Imaging studies reveal a right-sided empyema. Tube thoracostomy is performed and drains a large volume of pus; broad-spectrum antibiotics are continued. The patient’s fever subsequently improves but she now has difficulty raising her right arm above her head. When she pushes against a wall with outstretched arms, there is prominence of the right scapular angle. Which of the following muscles is most likely affected?
This patient has paralysis of the serratus anterior muscle, which originates on the first 8 ribs and inserts on the medial border of the scapula. It stabilizes and rotates the scapula upward, allowing complete abduction of the arm over the head. Paralysis results in inability to raise the arm over the head and protrusion (“winging”) of the medial border of the scapula when the outstretched arm is pushed forward against resistance.
Innervation of the serratus anterior is from the long thoracic nerve, which follows a lengthy course along the lateral chest wall. Injury to the nerve can occur during penetrating trauma or iatrogenically during axillary lymph node dissection or chest tube insertion.
Serratus anterior innervation
Innervation of the serratus anterior is from the long thoracic nerve, which follows a lengthy course along the lateral chest wall. Injury to the nerve can occur during penetrating trauma or iatrogenically during axillary lymph node dissection or chest tube insertion.
Serratus anterior actions
serratus anterior muscle, which originates on the first 8 ribs and inserts on the medial border of the scapula. It stabilizes and rotates the scapula upward, allowing complete abduction of the arm over the head.
Exocrine pancreas secretions
The exocrine pancreas secretes approximately 1 L of fluid, which consists of an aqueous portion and an enzymatic portion, into the duodenum daily. The acinar cells primarily contribute to the enzymatic portion and the ductal cells are responsible for producing the aqueous portion.
Pancreatic exocrine secretions contain fixed concentrations of sodium and potassium that are virtually identical to those of plasma. Levels of bicarbonate and chloride, however, vary with the pancreatic flow rate, which increases in response to the hormone secretin. During low flow, the ductal cells secrete an isotonic solution containing low bicarbonate concentrations and higher chloride concentrations. During high flow, the pancreas secretes an isotonic solution that is high in bicarbonate and low in chloride.
Delivery of acidic chyme to the duodenum stimulates mucosal endocrine cells (S cells) to release secretin, which in turn stimulates secretion of bicarbonate by the pancreatic ductal cells. As secretion of bicarbonate increases, luminal chloride concentration decreases. A chloride-bicarbonate exchanger on the apical surface of ductal cells helps maintain this inverse relationship.
An 18-year-old college student comes to the office due to severe anxiety and episodes of “heart pounding.” She witnessed a car accident with multiple fatalities 3 weeks ago. The patient awakes multiple times each night in a cold sweat and has trouble falling back asleep. During the day, she keeps seeing the accident and obsesses about steps she might have taken to help the injured. The patient has avoided leaving her home as any loud traffic sounds cause her to panic with a racing heart and dizziness. She has also felt sad and guilty for not helping more and finds it difficult to be around friends and family. The patient had to postpone her recent final exams because she found it impossible to study. She has no psychiatric or medical history. Which of the following is the most likely diagnosis?
Acute Stress Disorder because it has been less than one month, >1 month= PTSD
Acute Stress disorders features
- Anxiety associated with intrusive memories, nightmares, and arousal (sleep difficulty, poor concentration, exaggerated startle) is consistent with acute stress disorder (ASD).
- Avoidance of external reminders (outside traffic noises), impaired concentration, and negative mood are also characteristic of the disorder.
- Symptoms must last for >3 days and <1 month following trauma exposure.
- Patients typically have some form of intrusive re-experience (distressing memories, nightmares, flashbacks) and are preoccupied with negative thoughts about their role in the traumatic event.
- They may have dissociative experiences such as forgetting details of the event or feeling detached from reality.
Adjustment Disorder
- in adjustment disorder, intrusive recollections and avoidance behavior characteristic of ASD are not present.
- The stressor can be of any severity (eg, moving, divorce) and results in symptoms of anxiety and depression that do not meet the criteria for another psychiatric disorder.
Acute Stress Disorder vs Post-traumatic Stress disorder
- ASD is distinguished from post-traumatic stress disorder (PTSD) mainly by duration.
- Not all patients with ASD develop PTSD, but they do have a greater risk of doing so and should be monitored regularly.
- If the symptoms persist for >1 month and meet criteria for PTSD, the diagnosis is changed from ASD to PTSD.
Differential Diagnoses of Psychotic Disorders
Accurate diagnosis of primary psychotic disorders requires attention to the time frame and extent of psychotic symptoms.
Features of Brief psychotic disorder
- ≥1 days & <1 month,
- sudden onset,
- full return to function
Brief psychotic disorder is typically associated with sudden onset of psychotic symptoms lasting ≥1 day and <1 month, with full return to premorbid functioning
Schizophreniform disorder features
≥1 months & <6 months, same symptoms as schizophrenia, functional decline not required
Schizophrenia features
≥6 months (includes ≥1 months of active symptoms, can include prodromal & residual periods), requires functional decline
Schizoaffective disorder features
Mood episode with concurrent active-phase symptoms of schizophrenia + ≥2 weeks of delusions or hallucinations in the absence of prominent mood symptoms
Delusional disorder features
- ≥1 delusions & ≥1 months, no other psychotic symptoms, normal functioning apart from direct impact of delusions
- In delusional disorder, other psychotic symptoms (eg, hallucinations, disorganized speech and behavior) are not present. Apart from the impact of the delusion(s), behavior is not obviously bizarre and functioning is not markedly impaired.
A new screening test is positive for disease X in 250 out of 1,000 affected patients and in 100 out of 1,000 healthy controls. The screening test is then applied to a population where the disease prevalence is 10,000/100,000. How many false positives would be expected per 100,000 individuals in this population?
The screening test was incorrectly positive for disease X in 100 out of 1,000 healthy controls, corresponding to a false positive rate (FPR) of 10% (100/1,000). Note that this also means that the test correctly identified 900 out of the 1,000 healthy individuals as being healthy, corresponding to a specificity of 90% (900/1,000). The FPR, which is equal to (1 – specificity), is a characteristic of the screening test and does not change with disease prevalence (similar to sensitivity and specificity). In a population of 100,000 with a disease prevalence of 10,000/100,000, 10,000 will have the disease and 90,000 will not. When the same FPR is applied to these 90,000 healthy individuals, there will be 90,000 × 10% = 9,000 false positives per 100,000 individuals.
The solution can also be visualized using a 2 x 2 (contingency) table. Starting with a hypothetical population of 100,000 individuals, the prevalence of diseased individuals is given as 10,000; this is the total number of diseased individuals (last row in second column). Therefore, the total number of healthy (non-diseased) individuals is 100,000 – 10,000 = 90,000 (last row in third column). The screening test is falsely positive in 100 out of 1,000 non-diseased controls, so there will be 9,000 false positive test results for the 90,000 non-diseased patients.
The rest of the table can be completed as follows: The number of non-diseased patients who test negative is 90,000 – 9,000 = 81,000. The screening test is positive in 250 out of 1,000 diseased patients (sensitivity = 250/1,000 = 25%), so for 10,000 diseased patients, there will be 2,500 positive test results and 10,000 – 2,500 = 7,500 negative test results (second and third rows in second column).
A group of women between ages 30 and 40, all of whom have a point mutation in fibroblast growth factor receptor 2 (FGFR2), are followed for five years. Thirty of the women develop breast cancer during this period and 65 do not. A second group of women without the mutation is also followed for five years. Twenty women in this group develop breast cancer and 75 do not. Which of the following best describes the relative risk of breast cancer in women with the FGFR2 mutation?
1.5
The relative risk (RR) is defined as the risk of developing a certain endpoint in patients with a specific “exposure” (here, the mutation) divided by the risk in unexposed subjects. In the above scenario, the risk of developing breast cancer in subjects with the FGFR2 mutation is 30/(30+65) = 30/95, and the risk of developing breast cancer in subjects without the FGFR2 mutation is 20/(20+75) = 20/95. Thus, the RR is:
RR = (30/95)/(20/95) = 30/20 = 1.5
Relative Risk equation
Relative risk is calculated as the risk in exposed subjects divided by the risk in unexposed subjects.
Left side of table descriptor
Predictor (like exposure to risk factor or test result)
Top of Table descriptor
Outcome (like diseased or not)
Number Needed to Treat Equation
Absolute Risk Reduction Equation
Percentage indicating the actual difference in event rate between control & treatment groups
ARR = control rate – treatment rate
Relative risk reduction (RRR)
Percentage indicating relative reduction in the treatment event rate compared to the control group
RRR = ARR / control rate
Relative Risk (RR)
Ratio of the probability of an event occurring in the treatment group compared to the control group
RR = treatment rate / control rate
Number needed to treat (NNT)
Number of individuals who need to be treated to prevent a negative outcome in 1 patient
NNT = 1 / ARR
A 32-year-old man with a history of HIV is brought to the emergency department in January due to worsening headache and confusion. The patient had been acting inappropriately over the past 2 days. Today, he assaulted a coworker because she was “staring” at him. The patient takes antiretroviral medications, and his CD4 count was 400/mm3 a month ago. Temperature is 38.3 C (100.9 F). The patient appears lethargic. Pupils are equal and reactive to light and funduscopy is normal. The patient moves all extremities equally. There are no skin lesions. MRI of the brain reveals temporal lobe findings as shown in the image.
HSV Encephalitis
Pathogenesis of HSV Encephalitis
HSV-1 → olfactory tract → olfactory cortex (temporal lobe)
HSV Encephalitis presentation
- Fever, headache, seizures, aphasia, mental status/behavior changes
- Many patients also have signs of temporal lobe dysfunction such as olfactory hallucinations, anosmia, personality change, psychotic behavior, and/or aphasia.
Diagnosis of HSV Encephalitis
- Temporal lobe hemorrhage/edema on brain imaging
- Cerebrospinal fluid PCR for HSV
HSV Encephalitis Tx
Intravenous acyclovir
What is this?
Blood and Chocolate Agar cultures?
Blood and chocolate agar cultures are used to diagnose the leading causes of acute bacterial meningitis (eg, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae)
PML radiography
PML cause and features
The reactivation of JC virus, a polyomavirus, can cause progressive multifocal leukoencephalopathy in patients who have untreated AIDS. Manifestations usually arise over weeks (not days) and include altered level of consciousness, motor deficits, ataxia, and visual changes. MRI usually reveals multifocal areas of white matter demyelination.
Toxoplasmic encephalitis features
Toxoplasmic encephalitis is common in people who have AIDS with CD4 counts <100/mm3. It usually presents with headache, confusion, and fever. MRI of the brain typically shows multiple ring-enhancing lesions.
Toxoplasmic encephalitis radiography
MRI of the brain typically shows multiple ring-enhancing lesions.
A 19-year-old woman comes to the hospital due to 4 days of severe abdominal pain and nausea. She has also had reddish-brown discoloration of her urine but no dysuria or increased urinary frequency. Her boyfriend adds that she has become restless and irritable and has had several aggressive outbursts since she began to feel unwell. The patient had a similar episode at age 13 but has not had any symptoms since. She recently started taking combined oral contraceptives but takes no other medications. Her temperature is 37 C (98.6 F), blood pressure is 120/70 mm Hg, and pulse is 110/min and regular. On examination, she is anxious and her abdomen is soft with mild generalized tenderness on deep palpation. She has no skin rash. Which of the following conversions is most likely impaired in this patient?
A
Acute Intermittant Porphyria Pathophysiology
Enzymatic defects in the heme synthesis pathway (depicted in the question stem) result in porphyria, with defects in various enzymes causing different clinical manifestations. Typical manifestations of acute intermittent porphyria (AIP), which results from an autosomal dominant defect in porphobilinogen (PBG) deaminase (hydroxymethylbilane [HMB] synthase, uroporphyrinogen I synthetase) that can lead to elevated levels of PBG and aminolevulinic acid (ALA).
PBG deaminase deficiency by itself is typically not sufficient for development of AIP attacks (many affected patients never experience symptoms). When symptoms do occur, they generally develop in the setting of ALA synthase induction, which, combined with the inherited deficiency, causes excessive metabolite accumulation. ALA synthase induction can be due to increased progesterone (eg, puberty, contraceptives), certain medications (eg, cytochrome P450 inducers), alcohol use, smoking, or diet changes (eg, fasting).
Acute Intermittant Porphyria S&S
Typical clinical findings during an acute AIP attack include severe vague abdominal pain, nausea and vomiting, motor/sensory neuropathy, and neuropsychiatric manifestations (eg, insomnia, agitation).
A classic feature is port-wine colored urine that darkens on exposure to light and air (oxidation of excess PBG).
Cutaneous findings and photosensitivity are absent (as they are typically a result of porphyrinogen accumulation), and patients are symptom-free between attacks.
AIP is the second most common porphyria after porphyria cutanea tarda (PCT), caused by uroporphyrinogen decarboxylase (UROD) deficiency. UROD deficiency can be congenital or acquired (exposure to aromatic hydrocarbons, estrogen supplementation, hepatitis C). Cutaneous photosensitivity is the cardinal manifestation (Choice C).
Porphyria cutanea tarda cause
Porphyria cutanea tarda (PCT), caused by uroporphyrinogen decarboxylase (UROD) deficiency.
UROD deficiency can be congenital or acquired (exposure to aromatic hydrocarbons, estrogen supplementation, hepatitis C)
Porphyria Cutanea Tarda features
rare disorder characterized by painful, blistering skin lesions that develop on sun-exposed skin (photosensitivity)
Ferrochetolase deficiency
Deficiency of ferrochelatase, the last enzyme in the heme synthesis pathway, results in erythropoietic protoporphyria, the third most common type of porphyria, characterized by cutaneous photosensitivity beginning in early childhood. The activity of ferrochelatase is also decreased in lead intoxication.
ALA synthase inducers
4 listed
- Barbiturates
- Antiepileptics
- EtOH
- Smoking
