UW6 Flashcards
Question
The adrenal gland is made up of an outer cortex (divided into 3 zones) and an inner medulla:
- The zona glomerulosa is the outermost zone of the cortex and is composed of cells arranged in rounded or arched clusters (glomus is Latin for ball) that secrete mineralocorticoid hormones (primarily aldosterone).
- The zona fasciculata is the middle zone and contains foamy-appearing cells in columns (fascis is Latin for bundle or stack) that secrete glucocorticoid hormones (primarily cortisol).
- The zona reticularis is the inner zone of the cortex and contains cells in anastomosing cords (rete is Latin for net) that secrete androgens.
The adrenal medulla is sharply demarcated from the cortex and is composed of chromaffin cells with a deeply basophilic cytoplasm.
Chromaffin cells are modified neuroendocrine cells derived from the neural crest. They are stimulated by acetylcholine released by sympathetic preganglionic neurons and secrete catecholamines (80% epinephrine, 20% norepinephrine) directly into the bloodstream to amplify sympathetic nervous system activity.
Zona Glomerulosa location and function
The zona glomerulosa is the outermost zone of the cortex and is composed of cells arranged in rounded or arched clusters (glomus is Latin for ball) that secrete mineralocorticoid hormones (primarily aldosterone).
Zona Fasiculata location and function
The zona fasciculata is the middle zone and contains foamy-appearing cells in columns (fascis is Latin for bundle or stack) that secrete glucocorticoid hormones (primarily cortisol).
Zona Reticularis location and function
The zona reticularis is the inner zone of the cortex and contains cells in anastomosing cords (rete is Latin for net) that secrete androgens.
Identify
Adrenal medulla location and function
The adrenal medulla is sharply demarcated from the cortex and is composed of chromaffin cells with a deeply basophilic cytoplasm.
Chromaffin cells are modified neuroendocrine cells derived from the neural crest. They are stimulated by acetylcholine released by sympathetic preganglionic neurons and secrete catecholamines (80% epinephrine, 20% norepinephrine) directly into the bloodstream to amplify sympathetic nervous system activity.
Question
This infant likely had Potter sequence, which is characterized by pulmonary hypoplasia, flat facies, and lower limb deformity (eg, club foot). Potter sequence is caused by a urinary tract anomaly that leads to decreased fetal urine output. It is classically associated with bilateral renal agenesis but can occur secondary to other etiologies, including posterior urethral valves or fetal exposure to ACE inhibitors.
Because fetal urine is the main component of amniotic fluid, decreased fetal urine output can lead to low or absent amniotic fluid levels (ie, severe oligohydramnios). Inadequate amniotic fluid levels allow for increased external compression of the fetal face (flat facies) and extremities (eg, club foot). In addition, the umbilical cord is often compressed such that fetal heart rate abnormalities (eg, recurrent decelerations) are common during labor.
Amniotic fluid also provides the fluid and growth factors needed for fetal lung development. Therefore, neonates with Potter sequence have pulmonary hypoplasia due to the lack of normal alveolar distension by aspirated amniotic fluid. Both lungs are affected, and respiratory failure (ie, hypoxia) is the most common cause of death in affected infants.
Fetal exposure to ACE inhibitors and ARBs
Causes of bilateral renal agenesis
potter sequence
Posterior urethral valves
ACE inhibitor or ARBs exposure
Question
B.
Beta blockers are the preferred treatment for patients with chronic stable angina and hypertension. They relieve anginal symptoms by inhibiting sympathetic stimulation of the heart, reducing both heart rate and contractility. Because beta blockers reduce heart rate and blood pressure during rest and exercise, the onset of angina is avoided or delayed.
At low doses, atenolol is a selective β1 adrenergic antagonist. β1 receptors are found in cardiac tissue and on renal juxtaglomerular cells, but not in vascular smooth muscle. The β1 receptor is a G protein-coupled receptor (GPCR) associated with Gs, which increases intracellular cAMP levels. Blockade of the β1 receptor leads to decreased cAMP levels in cardiac and renal tissue without significantly affecting cAMP levels in vascular smooth muscle (Choices C and D).
GPCRs comprise a large family of 7 transmembrane domain receptors that activate intracellular second messenger systems. There are 2 principal second messenger systems involving GPCRs:
cAMP signaling pathway: The activated Gs α subunit activates the enzyme adenylyl cyclase, which catalyzes the conversion of ATP into cAMP. Elevated cAMP leads to the activation of protein kinase A. Conversely, the Gi α subunit inhibits adenylyl cyclase, thereby reducing cAMP levels.
Phosphatidylinositol signaling pathway: The activated Gq α subunit activates phospholipase C, which degrades membrane lipids into diacylglycerol (DAG) and inositol triphosphate (IP3). Protein kinase C is activated by DAG, and calcium is released from the sarcoplasmic reticulum under the influence of IP3.
(Choice A) Propranolol is a nonselective beta blocker that blocks both β1 and β2 adrenergic receptors. β2 receptors are found in vascular and bronchial smooth muscle. Blockade of β1and β2 receptors would therefore result in decreased cAMP levels in cardiac myocytes, renal juxtaglomerular cells, and vascular smooth muscle.
(Choice E) A medication such as diltiazem, a non-dihydropyridine calcium channel blocker, would not directly affect cAMP levels.
Educational objective:
β1 adrenergic receptors are found in cardiac tissue and on renal juxtaglomerular cells, but not in vascular smooth muscle. Selective blockade of the β1 receptor (eg, with atenolol) leads to decreased cAMP levels in cardiac and renal tissue without significantly affecting cAMP levels in vascular smooth muscle.
G-protein coupled receptors and their signal transducers:
α1
Gq
G-protein coupled receptors and their signal transducers:
α2
Gi
G protein–coupled receptors & their signal transducers:
β1
Gs
G protein–coupled receptors & their signal transducers:
β2
Gs
G protein–coupled receptors & their signal transducers
M1
Gq
G protein–coupled receptors & their signal transducers
M2
Gi
G protein–coupled receptors & their signal transducers
M3
Gq
G protein–coupled receptors & their signal transducers
D1
Gs
G protein–coupled receptors & their signal transducers
D2
Gi
G protein–coupled receptors cAMP pathway
cAMP signaling pathway: The activated Gs α subunit activates the enzyme adenylyl cyclase, which catalyzes the conversion of ATP into cAMP. Elevated cAMP leads to the activation of protein kinase A. Conversely, the Gi α subunit inhibits adenylyl cyclase, thereby reducing cAMP levels.
G protein–coupled receptors Phosphatidylinisotol signaling pathway
Phosphatidylinositol signaling pathway: The activated Gq α subunit activates phospholipase C, which degrades membrane lipids into diacylglycerol (DAG) and inositol triphosphate (IP3). Protein kinase C is activated by DAG, and calcium is released from the sarcoplasmic reticulum under the influence of IP
Question
E. Cryptococcyus Neoformans
Cryptococcus neoformans is a yeast that has an antiphagocytic polysaccharide capsule, a major virulence factor. The polysaccharide capsule appears as a clear, unstained zone with India ink and stains red with mucicarmine (as seen in this patient). Methenamine silver stain can identify the yeast forms, seen in tissue as round cells with narrow-based buds.
C neoformans usually affects immunocompromised patients (eg, kidney transplantation patients on chronic immunosuppression). It is a neurotropic fungus that is transmitted via the respiratory route and most commonly presents with subacute or chronic meningoencephalitis. Cryptococcal lung disease can occasionally cause pneumonia-like symptoms, including cough with scant sputum production, pleuritic chest pain, dyspnea, and hemoptysis. Chest x-ray findings are nonspecific (eg, infiltrates, nodules). Diagnosis is usually confirmed by identifying Cryptococcus in sputum, bronchoalveolar washings, or tissue samples.
(Choice A) Aspergillus fumigatus can cause pulmonary disease and invasive aspergillosis, most commonly in immunocompromised patients. However, microscopy typically shows septate hyphae.
(Choice B) Blastomyces dermatitidis can cause both lung disease and disseminated mycosis. Its microscopic appearance in tissue is that of a round yeast with broad-based budding and a thick, doubly reflective wall.
(Choice C) Candida albicans most commonly causes oropharyngeal, mucocutaneous, and esophageal disease. It rarely causes pneumonia. Microscopy typically shows budding yeast with pseudo-hyphae.
(Choice D) Coccidioides immitis causes lung disease in immunocompetent individuals and disseminated mycosis in immunocompromised patients. In tissue samples, it appears as large, irregularly sized, thick-walled spherules that contain small, round endospores.
(Choice F) Histoplasma capsulatum is a dimorphic fungus that causes tuberculosis-like pulmonary disease. It can also cause disseminated mycosis in immunocompromised patients. It is found intracellularly in tissue (within macrophages), appearing as small, ovoid, and budding yeast cells.
(Choice G) Rhizopus species typically causes rhino-orbito-cerebral infection but can cause pulmonary disease, predominantly in immunocompromised patients. Histology typically shows broad hyphae with irregular branching and rare septations.
Educational objective:
Cryptococcus neoformans is the only pathogenic fungus that has a polysaccharide capsule. The capsule appears red on mucicarmine stain and as a clear unstained zone with India ink.
Aspergillus fumigatus causes and histology
Aspergillus fumigatus can cause pulmonary disease and invasive aspergillosis, most commonly in immunocompromised patients. However, microscopy typically shows septate hyphae.
Blastomyces dermatitidis causes and histology
Blastomyces dermatitidis can cause both lung disease and disseminated mycosis.
Its microscopic appearance in tissue is that of a round yeast with broad-based budding and a thick, doubly reflective wall.
Candida albicans causes and histology
Candida albicans most commonly causes oropharyngeal, mucocutaneous, and esophageal disease. It rarely causes pneumonia.
Microscopy typically shows budding yeast with pseudo-hyphae.
Coccidioides immitis causes and histology
Coccidioides immitis causes lung disease in immunocompetent individuals and disseminated mycosis in immunocompromised patients.
In tissue samples, it appears as large, irregularly sized, thick-walled spherules that contain small, round endospores.
Histoplasma capsulatum causes and histology
Histoplasma capsulatum is a dimorphic fungus that causes tuberculosis-like pulmonary disease. It can also cause disseminated mycosis in immunocompromised patients. It is found intracellularly in tissue (within macrophages), appearing as small, ovoid, and budding yeast cells. (methenamine silver stain)
Rhizopus species causes and histology
typically causes rhino-orbito-cerebral infection but can cause pulmonary disease, predominantly in immunocompromised patients.
Histology typically shows broad hyphae with irregular branching and rare septations.
Histoplasma capsulatam stain
Methenamine silver
Question
B. Paramyxovirus
This child initially had fever, rhinitis, and pharyngitis, which are symptoms typical of an upper respiratory tract infection (URI). Most URIs (with or without pharyngitis) are caused by viruses, with roughly 15%-30% of childhood cases of pharyngitis and 5%-15% of adulthood cases of pharyngitis caused by bacteria.
When a child with a history of recent URI develops a brassy, barking cough and breathing difficulties, it is likely that acute laryngotracheitis (croup) has developed. The dyspnea associated with croup occurs when inflamed subglottic tissue obstructs the upper airway. The characteristic stridor of croup is a sign of significant upper airway obstruction. Croup is typically caused by the standard URI viruses, with the parainfluenza viruses (members of Paramyxoviridae) most commonly responsible.
Question
This patient with chronic kidney disease (CKD) has developed carpal spasm secondary to hypocalcemia. In CKD, reduced filtration and excretion of phosphorus causes hyperphosphatemia, which induces hypocalcemia through the following mechanisms:
Released phosphate binds to free calcium and precipitates in soft tissues (which, over the long term, can lead to vascular calcification and stiffness)
Increased serum phosphate triggers the release of fibroblast growth factor 23 from bone, which acts to lower phosphate levels in part by inhibiting renal expression of 1-alpha hydroxylase. This reduces production of 1,25-hydroxyvitamin D (calcitriol), leading to reduced intestinal calcium absorption
Hypocalcemia is also worsened by the progressive loss of functioning renal tissue in CKD, which further reduces calcitriol synthesis.
Hypocalcemia can cause alterations in cellular membrane potentials and neuromuscular excitability. Manifestations include muscle cramps, Chvostek (facial twitching elicited by tapping on the facial nerve) and Trousseau (carpal spasm triggered by inflation of a blood pressure cuff around the arm) signs, hyperreflexia, QTc prolongation, and seizures.
(Choice B) The hypocalcemia and hyperphosphatemia that occur in patients with CKD stimulate secretion of parathyroid hormone (ie, secondary hyperparathyroidism). By contrast, hypoparathyroidism is usually due to autoimmune disease or iatrogenic injury during thyroid surgery and is not a common finding in CKD.
(Choice C) Serum calcium is composed of an ionized free calcium fraction and a protein-bound (largely to albumin) fraction; only ionized calcium is metabolically active. Hypoalbuminemia can occur in patients with nephrotic syndrome (eg, this patient with focal segmental glomerulosclerosis). However, although hypoalbuminemia lowers the bound fraction (and therefore total serum calcium), ionized calcium remains normal, and patients do not experience hypocalcemic symptoms.
(Choice D) Fibroblast growth factor 23 levels are usually low in patients with normal phosphate metabolism but are increased in patients with renal failure in response to hyperphosphatemia.
(Choice E) Vitamin D toxicity can occur in food faddists, patients with mental illness, and those inadvertently treated with excessive doses of vitamin D. However, this causes hypercalcemia, not hypocalcemia.
Educational objective:
In chronic kidney disease, reduced excretion of phosphate can cause hyperphosphatemia. This induces hypocalcemia directly by binding free calcium and depositing in tissues, and indirectly by triggering fibroblast growth factor 23 secretion (decreases calcitriol production and intestinal calcium absorption). The resulting hypocalcemia can manifest as neuromuscular excitability (eg, carpal spasm).
Question
C. Increases circulating Von Willebrand Factor
Question
A. A specific human leukocyte antigen Class I allele
Ankylosing spondylitis is a chronic inflammatory disorder of the sacroiliac joints and axial skeleton. It is most common in young and middle-aged men and presents with morning stiffness and low back pain. Ankylosing spondylitis is characterized by destruction of articular cartilage with resulting stiffness and fusion of axial joints. The sacroiliac joints are often tender to palpation, and the spine may have decreased range of motion. X-ray of the sacroiliac joints may reveal erosions, sclerosis, and narrowing; ultimately fusion of the joint spaces. Spine x-rays reveal sclerosis, ligamentous calcification, and vertebral fusion (“bamboo spine”).
Ankylosing spondylitis, reactive arthritis, arthritis associated with inflammatory bowel disease, and psoriatic arthritis are seronegative spondyloarthropathies, so-called due to the absence of serum rheumatoid factor. Patients with these diseases have a higher incidence of the human leukocyte antigen (HLA) B27 allele, which encodes a specific HLA class I molecule, compared to the general population (although most patients with HLA B27 will not develop spondyloarthropathies).
(Choice B) Class I HLA proteins (eg, HLA B27) are expressed by all nucleated cells and present endogenous antigens to CD8+ cytotoxic T cells. By contrast, HLA class II proteins (eg, DR, DP, DQ alleles) are expressed by antigen-presenting cells (eg, macrophages, dendritic cells) and present predominantly foreign antigens to CD4+ helper T cells. Conditions associated with specific HLA class II alleles include rheumatoid arthritis, type I diabetes mellitus, and celiac disease.
(Choice C) Rheumatoid factor (IgM antibodies against self IgG) is present in the majority of patients with rheumatoid arthritis and may be seen in a variety of other autoimmune diseases as well as in some healthy individuals.
(Choice D) Complement component deficiencies are associated with recurrent infections and systemic lupus erythematosus.
(Choice E) IgA deficiency causes recurrent mucosal and respiratory infections as well as anaphylactic reactions after transfusion of blood products.
Educational objective: The seronegative spondyloarthropathies include ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and arthritis associated with inflammatory bowel disease. Individuals expressing HLA B27 (a specific HLA class I molecule) are at increased risk for the seronegative spondyloarthropathies.
Diabetes insipidus fluid volume and osmolarity
Hyperosmolar volume contraction
Primary polydipsia fluid volume and osmolarity
hyposmolar volume expansion
SIADH fluid volume and osmolarity
Hypoosmolar volume expansion
Features of radiation-induced lung injury
Question
A. Autism
This patient’s behavior is most consistent with mild, high-functioning autism spectrum disorder (ASD). Patients diagnosed with ASD later in childhood and adolescence frequently have normal or near-normal language and intellectual ability and come to clinical attention when social and academic demands increase, exposing a lack of flexibility and social skill deficits (more severe ASD is usually diagnosed by age 5). Key features of ASD include deficits in social communication and reciprocal social interactions as well as restricted, repetitive interests and stereotyped behaviors.
This patient’s lack of friends, social isolation, insistence on sameness, intensely fixated interests, and trouble taking turns in conversation are characteristic. Patients with autism have difficulty interpreting and responding appropriately to nonverbal aspects of communication. Abnormal eye contact, stilted, overly formal speech, abnormal sensory sensitivity, and unusual repetitive movements (hand flapping, rocking) are other common findings.
(Choice B) Obsessive-compulsive disorder may also present with obsessive interests and insistence on routines. However, this patient lacks the intrusive obsessional thoughts and compulsive rituals performed in response to these thoughts required for this diagnosis (eg, thoughts of contamination leading to cleaning rituals).
(Choices C and D) Personality disorders are not diagnosed when the behavior is better explained by another mental disorder and are generally not diagnosed before age 18. Patients with obsessive-compulsive personality disorder are preoccupied with orderliness and control but do not have deficits in social communication. Patients with schizoid personality disorder are socially isolated and disinterested in relationships, but do not exhibit the restricted interests and repetitive patterns seen in ASD.
(Choice E) Separation anxiety disorder is characterized by developmentally inappropriate and excessive anxiety related to separation from the primary attachment figure.
(Choice F) Patients with social anxiety disorder typically have normal communication skills and an interest in socializing, but they avoid social situations due to fear of being judged. In patients with ASD, social anxiety is related to their lack of social skills.
Educational objective:
Patients with milder forms of autism spectrum disorder frequently have normal language and cognitive development. Characteristic features include deficits in social communication and reciprocal social interactions, restricted interests, and behavioral rigidity that become more apparent as social and academic demands increase.
Question
E.
This patient’s history of vomiting and diarrhea and physical examination findings of tachycardia, dry mucous membranes, and decreased skin turgor are consistent with moderate to severe hypovolemia. Vomiting and diarrhea cause gastrointestinal losses of both sodium and water from the extracellular space with a consequent decrease in plasma volume. Because red blood cells and proteins such as albumin are relatively large and trapped intravascularly, these blood components become concentrated, leading to increased hematocrit and increased serum albumin. Such hemoconcentration can be a clue to hypovolemia caused by salt and/or water depletion; however, it does not occur with hypovolemia due to acute blood loss because red blood cells and albumin are also depleted.
In the setting of hypovolemia, the kidneys respond by increasing sodium reabsorption to increase circulating blood volume. This increased sodium reabsorption occurs in both the distal renal tubule via increased aldosterone activity and the proximal renal tubule through poorly understood mechanisms. Uric acid absorption is closely tied and directly related to sodium absorption in the proximal renal tubule; therefore, there is typically increased serum uric acid in the setting of hypovolemia. Although uric acid levels are not typically collected in the management of hypovolemia, the relationship between hypovolemia and serum uric acid level has clinical application in that hypovolemia increases the risk of acute gout flares.
Educational objective:
Hypovolemia due to loss of sodium and/or water causes increased concentration of red blood cells (ie, hematocrit) and albumin as both of these blood components are trapped within the intravascular space. Hypovolemia also triggers increased absorption of uric acid in the proximal renal tubule, resulting in an increased serum uric acid level.
Question
The glomerular filtration rate (GFR) depends on the interplay of hydrostatic and oncotic pressures in the glomerular capillaries and Bowman’s space. The GFR increases with higher glomerular hydrostatic pressure and decreases with increasing Bowman’s capsule hydrostatic pressure or higher glomerular capillary oncotic pressure. Acute ureteral obstruction increases hydrostatic pressure proximal to the constriction. This pressure rise is transmitted back to the Bowman’s space, resulting in decreased GFR.
The filtration fraction (FF) is the portion of the renal plasma flow (RPF) that is filtered from the glomerular capillaries into Bowman’s space (ie, the GFR:RPF ratio). With acute ureteral obstruction (first 12 hours), the RPF may transiently increase; however, with time, efferent arteriolar constriction (in response to reduced GFR) will decrease RPF. Even at later stages, though, the GFR remains depressed to a greater extent than the RPF, resulting in reduced FF.
Educational objective:
Acute ureteral constriction or obstruction decreases the glomerular filtration rate and filtration fraction.
Question
Question
C. .03 and .90
Parameters of hypovolemic shock
Parameters of cardiogenic shock
Parameters of obstructive shock
Parameters of distributive shock
Question
Cranial nerve reflexes
Pupillary Light Reflex effect, afferent and efferent
Corneal Reflex effect, afferent and efferent
Jaw-jerk Reflex effect, afferent and efferent
Vestibulo-ocular reflex effect, afferent and efferent
Carotid Sinus Reflex effect, afferent and efferent
Cough reflex effect, afferent and efferent
Gag reflex effect, afferent and efferent
Question
D.
Many patients with hypertrophic cardiomyopathy (HCM) have dynamic left ventricular outflow tract (LVOT) obstruction that, when severe, can drastically limit cardiac output. The degree of LVOT obstruction is worsened by conditions that decrease left ventricular (LV) blood volume; therefore, hemodynamics should be optimized to encourage high LV blood volume throughout the cardiac cycle.
High LV end-diastolic volume (ie, high preload) is encouraged by adequate hydration and avoidance of venous dilators (eg, nitroglycerin). In addition, low heart rate lengthens diastolic filling time to increase end-diastolic volume.
High LV end-systolic volume is encouraged by relatively low stroke volume. Both low contractility and high afterload (ie, the pressure the left ventricle must contract against) decrease the amount of blood ejected during systole, allowing for more effective cardiac output by minimizing the degree of LVOT obstruction.
Beta blockers (eg, metoprolol) are highly useful in treating HCM because they decrease both heart rate and LV contractility to encourage high LV blood volume and minimize LVOT obstruction.
Educational objective:
The degree of left ventricular (LV) outflow tract obstruction in hypertrophic cardiomyopathy is minimized by relatively high LV blood volume. High LV end-diastolic blood volume (ie, preload) is encouraged by adequate hydration and low heart rate. High LV end-systolic volume is encouraged by relatively low stroke volume, which is facilitated by high LV afterload and low LV contractility.
