Uworld Pathophysio1

Question 1

—— myopathy presents with myalgias, proximal muscle weakness, elevated creatine kinase levels, and delayed relaxation of deep tendon reflexes. The diagnosis can be confirmed with an elevated TSH level. Other common causes of myopathy with elevated creatine kinase levels include inflammatory myopathies, muscular dystrophies, and HMG-CoA reductase inhibitors.

Answer 1

Hypothyroid

Question 2

Subacute —– thyroiditis is characterized by disruption of follicles and a mixed cellular infiltrate with occasional multinucleated giant cells. Patients may have hyperthyroidism but typically have a painful, tender thyroid gland and high levels of thyroglobulin due to destructive thyroiditis

Answer 2

granulomatous (de Quervain)

Question 3

—— cancer is a neuroendocrine tumor that arises from calcitonin-secreting parafollicular C cells. Microscopy shows nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits (derived from calcitonin). Clinical features include diarrhea, flushing, and thyroid nodules, but TSH and free T4 are normal

Answer 3

Medullary thyroid

Question 4

—– disease presents with a diffusely enlarged thyroid gland associated with hyperthyroidism, exophthalmos, and pretibial myxedema. The thyroid follicular epithelium is tall and crowded with hyperactive reabsorption, causing scalloping around the edges of the colloid. High serum levels of thyroglobulin would be seen due to increased thyroid metabolic activity.

Answer 4

Graves disease

Question 5

Exogenous —-thyroidism is characterized by elevated free thyroxine (T4), suppressed TSH, and low/undetectable thyroglobulin. It can occur with surreptitious levothyroxine abuse, use of animal-sourced thyroid supplements, and erroneous dosing of thyroid replacement therapy. Over time, the lack of TSH stimulation causes the thyroid follicles to become atrophic.

Answer 5

hyperthyroidism

Question 6

—– hypersensitivity is most commonly seen in elderly men and involves an exaggerated vasovagal response to tactile stimulation of carotid sinus baroreceptors (eg, adjusting a shirt collar or necktie). The resulting increase in parasympathetic output leads to a prolonged sinus pause that contributes to the excessive drop in blood pressure, leading to transient loss of cerebral perfusion that manifests as presyncope (eg, lightheadedness) or syncope

Answer 6

Carotid sinus

Question 7

Malabsorption is a syndrome of impaired intestinal digestion and absorption. Fats are typically the most severely affected macronutrient in generalized malabsorption, and testing the stool for fat (eg, with —– stain) is the most sensitive strategy for screening for malabsorptive disorders.

Answer 7

Sudan III

Question 8

New-onset odynophagia in the setting of chronic gastroesophageal reflux disease should raise suspicion for ——-. Diagnosis is made by upper endoscopy.

Answer 8

erosive esophagitis with esophageal ulcers

Question 9

Atrioventricular nodal reentrant tachycardia is the most common type of paroxysmal supraventricular tachycardia, resulting from abnormal conduction through 2 distinct atrioventricular nodal pathways. ECG typically demonstrates a ——- with a regular rhythm and buried (not visible) P waves.

Answer 9

narrow QRS complex tachycardia

Question 10

Malabsorption caused by celiac disease can lead to vitamin D deficiency. Patients have —– serum phosphorus, —– serum parathyroid hormone (secondary hyperparathyroidism), and —- serum calcium

Answer 10

decreased serum phosphorus

increased serum parathyroid hormone (secondary hyperparathyroidism),

low (or normal) serum calcium

Question 11

patient with diarrhea, weight loss, and a positive tissue transglutaminase antibody assay has ——disease, an immune-mediated hypersensitivity to dietary gluten. —- disease is characterized by villous atrophy in the small intestine, leading to malabsorption of dietary fats and fat-soluble vitamins (ie, A, D, E, K). The resulting vitamin D deficiency can present as rickets in children and osteomalacia in adults.

Answer 11

celiac

Question 12

Anaphylaxis can cause distributive shock due to widespread release of inflammatory mediators (eg, histamine) that leads to massive peripheral vasodilation. Arteriolar vasodilation —– systemic vascular resistance to cause hypotension, and venular vasodilation —— central venous pressure and pulmonary capillary wedge pressure. Cardiac output is often increased in early distributive shock due to reduced SVR and a baroreceptor reflex–mediated increase in heart rate

Answer 12

decreases

Question 13

Neonatal hypoglycemia is common in infants of diabetic mothers. The pathophysiology involves maternal hyperglycemia, which in turn causes fetal hyperglycemia and compensatory hyperfunctioning of the ——. After birth, persistently elevated insulin levels lead to transient hypoglycemia.

Answer 13

pancreas (ie, hyperinsulinemia)

Question 14

Increased bone resorption in primary —— leads to osteoporosis primarily involving the cortical bone of the appendicular skeleton. The cortical thinning appears radiologically as subperiosteal erosions. More advanced disease can present as osteitis fibrosa cystica (ie, granular decalcification of the skull, osteolytic cysts, and brown tumors).

Answer 14

hyperparathyroidism

Question 15

Asymptomatic left ventricular systolic dysfunction is a common stage in the progression of heart failure. Neurohormonal mechanisms, including the sympathetic nervous system and renin-angiotensin-aldosterone system, help maintain the asymptomatic period by increasing volume retention and peripheral resistance to maintain organ perfusion. There will be —- levels angio2, NE and ANP

Answer 15

increased

Question 16

Hyperprolactinemia suppresses secretion of GnRH, which leads to reduced —- in women. Low estrogen levels are a risk factor for accelerated bone loss.

Answer 16

estrogen

Question 17

Because of the pulmonary location of angiotensin conversion, levels of angiotensin II are higher in the pulmonary —- (on the way out of the lungs) than in the pulmonary artery (on the way into the lungs).

Answer 17

vein

Question 18

The right ventricle (RV) is relatively protected from myocardial infarction (MI), and contractile function of the RV usually returns to normal following MI. Factors contributing to this protection include ——-, perfusion throughout the cardiac cycle, and heightened ischemic preconditioning.

Answer 18

relatively small muscle mass with high capacity to increase oxygen extraction

Question 19

—– disease is an immune-mediated disorder triggered by dietary gluten that causes small-bowel malabsorption. Because the proximal small bowel is primarily affected, iron deficiency leading to microcytic anemia is common. Histopathology is characterized by intraepithelial lymphocytosis, loss of intestinal villi, and mucosal atrophy.

Answer 19

Celiac

Question 20

Sex hormones promote both growth and —– closure; hence, precocious puberty may result in a shorter stature, despite an initial growth spurt.

Gigantism is caused by excessive pituitary production of growth hormone; these patients achieve enormous heights because, unlike excessive sex steroids, excessive —- does not lead to premature closure of the epiphysis.

Answer 20

epiphyseal plate

IGF-1

Question 21

Pulmonary infection (eg, community-acquired pneumonia, tuberculosis) causes pleural effusion primarily via an inflammatory increase in vascular and pleural membrane permeability. Such effusions are exudative by Light criteria, typically with relatively high pleural fluid —- and —– concentrations. Tuberculosis pleural effusions typically demonstrate a lymphocyte-predominant leukocyte pattern.

Answer 21

high pleural fluid protein and lactate dehydrogenase

Question 22

Chronic obstructive pulmonary disease is a combination of emphysema and chronic bronchitis and commonly presents with progressive dyspnea and recurrent upper respiratory infections. Bronchial obstruction and alveolar destruction cause air trapping that manifests on pulmonary function testing as —–forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Residual volume and total lung capacity are ——

Answer 22

decreased forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio

Residual volume and total lung capacity are increased

Question 23

Intrinsic factor (IF) is a glycoprotein that is normally secreted by parietal cells in the stomach and is necessary for the absorption of vitamin B12 in the ileum. Patients who have undergone a total gastrectomy require lifelong —– supplementation due to inability to produce IF.

Answer 23

vitamin B12

Question 24

Decreased cardiac output in heart failure triggers neuroendocrine compensatory mechanisms to maintain organ perfusion; however, the compensatory mechanisms are maladaptive over the long term. Increased sympathetic output and activation of the renin-angiotensin-aldosterone system stimulate vaso—- and volume retention, compounding the hemodynamic stress on an already failing heart and creating a vicious cycle of decompensation.

Answer 24

vasoconstriction

Question 25

**Atheroembolic disease typically occurs after an invasive vascular procedure** due to mechanical dislodgement of atherosclerotic plaque, resulting in the showering of **cholesterol-rich microemboli** into the circulation. **----- in affected vessels are diagnostic.** Commonly involved organs include the **kidneys (eg, acute kidney injury),** skin (eg, blue toe syndrome, livedo reticularis), gastrointestinal tract (eg, bleeding, infarction), and CNS (eg, stroke, amaurosis fugax)

Answer 25

**Needle-shaped cholesterol clefts**

Question 26

**--------** is a **chronic autoimmune liver disease** characterized by destruction of small and midsized intrahepatic bile ducts with resulting **cholestasis.** It is most common in **middle-aged women** and is frequently associated with other autoimmune disorders (eg, Sjögren syndrome, rheumatoid arthritis). Clinical features include **fatigue, itching (pruritus), and hepatomegaly.** Serum **alkaline phosphatase is elevated**, and **_antimitochondrial antibody titers are positive_** in most cases. Biopsy findings in PBC typically show **patchy lymphocytic inflammation, leading to granulomatous destruction of intrahepatic bile ducts** (ie, florid duct lesion), with **necrosis and micronodular regeneration of periportal tissues.**

Answer 26

**Primary biliary cholangitis**

Question 27

The **work of breathing is minimized in patients with increased elastic resistance** (eg, pulmonary fibrosis) when their r**espiratory rate is ----- and tidal volume is ----**(fast, shallow breaths). In contrast, patients with diseases that **increase airflow resistance (eg, asthma, chronic obstructive pulmonary disease)** breathe at a **lower respiratory rate and higher tidal volume** (slow, deep breaths) to minimize the work of breathing.

Answer 27

high low

Question 28

Advanced hypoxic lung disease (eg, **chronic obstructive pulmonary disease, interstitial lung disease, obesity hypoventilation syndrome**) is a common cause of **_pulmonary -------_** The increase in pulmonary arterial pressure mainly results from chronic and diffuse hypoxic **vasoconstriction**, with a lesser degree of vascular remodeling than in (primary) pulmonary arterial hypertension.

Answer 28

**_hypertension_** (ie, **increased right ventricular afterload**).

Question 29

Patients with **multiple sclerosis** often develop a **spastic bladder** a few weeks after developing an acute lesion of the spinal cord. These patients present clinically with **increased urinary frequency and urge incontinence**. Urodynamic studies show the presence of **bladder ------**

Answer 29

hypertonia

Question 30

**Multiple myeloma** is a plasma cell malignancy associated with purely **radiolucent (osteolytic) bone** lesions due to the **stimulation of -------** and the inhibition of osteoblasts. Myeloma cells stimulate ------ development by secreting RANK-ligand and destroying osteoprotegerin, which increases RANK activity and results in osteoclast differentiation.

Answer 30

osteoclasts

Question 31

The absence of normal enteral stimulation in patients receiving **total parenteral nutrition** leads to decreased **-----** release, biliary stasis, and **_increased risk of gallstones._** Resection of the ileum can also increase the risk of gallstones due to disruption of normal enterohepatic circulation of bile acids.

Answer 31

**cholecystokinin**

Question 32

The 2 most common cardiac abnormalities seen in **Marfan Syndrome patients** are **_mitral valve prolapse and cystic medial degeneration of the aorta_**. In more than 75% of MFS patients, cystic medial degeneration of the aorta results in aneurysmal dilation. If untreated, this can cause **aortic ----,** the most common cause of death in MFS patients

Answer 32

dissection

Question 33

**Loss of cardiomyocyte contractility** occurs within --- **seconds** after the onset of total ischemia. When **ischemia lasts less than 30 minutes, restoration of blood flow leads to _reversible_ contractile dysfunction** (myocardial stunning), with contractility gradually returning to normal over the next several hours to days. However, after about 30 minutes of total ischemia, ischemic injury becomes irreversible.

Answer 33

60

Question 34

**Pheochromocytomas** are catecholamine-secreting tumors arising from the **---- cells of the adrenal medulla or extra-adrenal sympathetic chain**, and typically present with **severe hypertension**. Pheochromocytomas **stimulate the renin-angiotensin system due to high circulating catecholamine levels,** and are associated with **tachycardia** and symptoms of catecholamine excess (eg, **sweating, palpitations, headache**).

Answer 34

**chromaffin**

Question 35

**Primary hyperaldosteronism** (PH), a very common cause of **_secondary hypertension_**. PH is usually due to **increased secretion of mineralocorticoids from bilateral nodular hyperplasia** of the adrenal **zona ----** or an **aldosterone-producing adrenal adenoma (Conn syndrome).**

Answer 35

glomerulosa The main effect of aldosterone is to stimulate absorption of sodium and excretion of potassium and hydrogen ions in the renal collecting tubules. Aldosterone secretion from the zona glomerulosa is normally regulated by angiotensin II and potassium levels. **Overproduction of aldosterone can result in sodium retention, hypertension, and feedback suppression of the renin-angiotensin system (ie, very low renin activity).** Some patients also develop **metabolic alkalosis and hypokalemia**, which can be exacerbated by increased distal tubule sodium delivery (eg, diuretics, increased sodium intake). **Symptomatic hypokalemia may cause muscle weakness, cramps, and, occasionally, rhabdomyolysis and cardiac arrhythmias.**

Question 36

**----- neuropathy** is common in type 1 diabetics and can cause **overflow incontinence** due to inability to sense a full bladder and **incomplete emptying.****Increased Postvoid residual**or catheterization can confirm**inadequate bladder emptying.**

Answer 36

**Diabetic autonomic**

Question 37

**Patients with cystic fibrosis** have thick, viscous mucus that accumulates in the airways and promotes colonization of bacteria, particularly **Pseudomonas**. This **gram-negative rod** can produce **biofilms**, which act as a protective matrix that allows bacterial **----** to develop, causing persistent infection

Answer 37

macrocolonies

Question 38

**5-Alpha reductase inhibitors (eg, finasteride, dutasteride**) are used in the treatment of **benign prostatic hyperplasia.** These medications block the conversion of **testosterone to dihydrotestosterone**; the excess testosterone is then available for conversion to **estrogens** (eg, estradiol) by aromatase, which can lead to -----

Answer 38

gynecomastia

Question 39

**---- heart** refers to physiologic cardiac adaptations that improve cardiac function in response to **high-level endurance training.** There is predominant **left ventricular (LV) eccentric hypertrophy** with a small component of concentric hypertrophy, leading to an overall **increase in LV mass, enlarged LV cavity size, slightly increased LV wall thickness, and decreased resting heart rate.**

Answer 39

**Athlete's**

Question 40

**Dubin-Johnson syndrome** is a benign disorder characterized by **defective hepatic excretion of bilirubin glucuronides** across the canalicular membrane, resulting in **direct hyperbilirubinemia and jaundice.** Grossly, the **liver appears black** due to impaired excretion of ----- metabolites, which histologically appear as dense **pigments within lysosomes.**

Answer 40

epinephrine

Question 41

**Hypovolemia** triggers a variety of compensatory mechanisms to improve tissue perfusion. These include **activation of the renin-angiotensin-aldosterone system** (resulting in **--- aldosterone and endothelin release**), **increased vasopressin release**, and **increased sympathetic tone**

Answer 41

**increased**

Question 42

**-------** is marked by widespread activation of the **coagulation cascade**, leading to **excessive thrombin production** and formation of **microthrombi**. Subsequent conversion of plasminogen to plasmin results in **increased fibrinolysis** to clear the thrombi. Laboratory studies show a consumption of clotting factors (**prolonged PT/PTT**) and **platelets (thrombocytopenia)** and signs of excessive fibrinolysis (eg, elevated D-dimer).

Answer 42

**Disseminated intravascular coagulation**

Question 43

Patients with **severe iron deficiency anemia** (IDA) typically have evidence of **hypochromic, microcytic erythrocytes** on peripheral blood smear with poikilocytosis. Laboratory studies will reveal **low red blood cell count, low hepcidin, and ---- transferrin**. Although **erythropoietin is markedly elevated** in IDA, there is not enough iron to efficiently generate erythrocytes; therefore, **-----** count is low.

Answer 43

**high transferrin** reticulocyte

Question 44

---- is characterized by **medullary** thyroid cancer, **pheochromocytomas,** **mucosal neuromas** (ex multiple 4- to 8-mm soft papules on the lips and tongue), and **marfanoid habitus.** mutatation in **RET** pro-oncogene

Answer 44

MEN2B

Question 45

**febrile**, ill-appearing patient with **respiratory distress who is in the tripod position** likely has **_epiglottitis_**, a rare, potentially fatal infection most commonly caused by **Haemophilus influenzae type b**. Edema of the epiglottis can cause laryngeal obstruction that leads to **inspiratory ---**

Answer 45

stridor.

Question 46

**-------,** presents with **jaundice, dark urine, and acholic stools (pale/clay colored) in the _first 2 months of life_** due to **conjugated hyperbilirubinemia**. Biopsy reveals **intrahepatic bile duct proliferation, portal tract edema, and fibrosis.** ## Footnote Physical examination may also reveal **firm hepatomegaly due to inflammation.** Laboratory findings, including elevated direct bilirubin and **gamma-glutamyl transferase**, are consistent with cholestasis.

Answer 46

**Biliary atresia,** or **obstruction of extrahepatic bile ducts**

Question 47

**Neutrophil elastase** is released by both neutrophils and macrophages and is the **primary protease responsible for extracellular _elastin degradation_.** The **major serum inhibitor of elastase is alpha-1 antitrypsin (AAT).** In this study, the patients whose serum is unable to inhibit elastin degradation likely have **AAT deficiency,** a condition characterized by **early-onset panacinar emphysema** due to the unopposed action of neutrophil elastase on alveolar walls. ---- **exposure dramatically accelerates the development of emphysema in patients with AAT** deficiency by inducing inflammation

Answer 47

**Tobacco**

Question 48

Initial management of **_Transposition of the great arteries_** must ensure **mixing of oxygenated and deoxygenated blood.** For example, administration of **----- maintains patency of the ductus arteriosus.** Balloon atrial septostomy, which **opens or widens the foramen ovale**, may also be performed to allow for mixing at the atrial level and typically **improves oxygen saturation immediately.**

Answer 48

**prostaglandin E1**

Question 49

**Pulsus paradoxus** is defined by a **decrease in systolic blood pressure of \>10 mm Hg with inspiration.** It is most commonly **seen in patients with -----** but can also occur in s**evere asthma, chronic obstructive pulmonary disease, and constrictive pericarditis**

Answer 49

cardiac tamponade

Question 50

**Stable angina** results from fixed **coronary -----** that limits blood flow to downstream myocardium, preventing the myocardial oxygen supply from increasing during exertion. **_Dobutamine_** mimics the effects of **exercise** and increases myocardial oxygen demand; it can be used during stress testing to **provoke areas of ischemic myocardium,** which can be recognized on imaging by a localized and transient decrease in contractility (ie, wall motion defect) (**decrease in ejection fraction).**

Answer 50

**artery stenosis**

Question 51

Gigantism in kids is from excessive production of what?

Answer 51

IGF-1 from liver

Question 52

**Prolonged, untreated Obstructive Sleep Apnea** can cause **pulmonary ------ and ----- heart failure.** Most patients with OSA will develop **systemic hypertension** due to c**hronic sympathetic stimulation and elevated plasma norepinephrine levels.**

Answer 52

pulmonary hypertension and right heart failure

Question 53

Patients with **severe emphysema** typically have **chronic CO2 retention** leading to chronic r**espiratory ----** with **metabolic compensation** (high PaCO2, compensatory **high bicarbonate**, slightly acidic pH), often accompanied by **hypoxemia** (PaO2\<75 mm Hg on room air).

Answer 53

respiratory acidosis

Question 54

**Thrombotic thrombocytopenic purpura** is a thrombotic microangiopathy resulting in microangiopathic **----- anemia** and **thrombocytopenia**, findings that are essential for making the diagnosis. It is triggered by severe deficiency in **-----** levels.

Answer 54

**hemolytic anemia** **ADAMTS13**

Question 55

**----- syndrome** causes **infertility** characterized by primary hypogonadism (**elevated FSH and LH, low testosterone**) and **azoospermia**. Other findings include **long lower extremities; small, firm testes; and gynecomastia.**

Answer 55

**Klinefelter syndrome (47,XXY)**

Question 56

Nonclassic congenital adrenal hyperplasia is due to **mild deficiency of 21-hydroxylase**, an enzyme that converts **progesterone to ------** and **17-hydroxyprogesterone to 11-deoxycortisol.** In **adolescent girls,** it presents with signs of hyperandrogenism (eg, **hirsutism, acne, menstrual irregularities)** as well as **_increased 17-hydroxyprogesterone_** and **testosterone levels**

Answer 56

progesterone to 11-deoxycorticosterone

Question 57

Chronic **-----** causes a **reduction in diastolic blood pressure** and a compensatory **increase in left ventricular stroke volume**. These changes create a high-amplitude, rapid rise-rapid fall pulsation (ie, **widened pulse pressure)** and the other characteristic findings (eg, **head bobbing, "pistol-shot" femoral pulses**).

Answer 57

**aortic regurgitation**

Question 58

During **pregnancy**, increased metabolic demands lead to multiple physiologic cardiovascular changes, including **decreased systemic vascular resistance** and **increased blood volume**. These changes cause **---- preload and ---- afterload**, resulting in **increased stroke volume and cardiac output**. H**eart rate also gradually increases** during pregnancy and is the major contributor to increased cardiac output in late pregnancy.

Answer 58

**increased preload** **decreased afterload**

Question 59

Bronchial challenge testing is a highly sensitive but nonspecific measure that can help **exclude a diagnosis of asthma**. A provocative stimulus (typically aerosolized **_methacholine_**) is administered at increasing concentrations to **induce bronchoconstriction**. **Patients with asthma are hyperresponsive** to this stimulus and **_experience a decline in ---- at lower doses_** than nonasthmatics.

Answer 59

**_FEV1_**

Question 60

**Emphysema** from any cause leads to **increased total lung capacity** as the lungs hyperinflate, **decreased FEV1/FVC ratio**, and **----- DLCO** (diffusing capacity for carbon monoxide) due to destruction of alveoli and adjoining capillary beds

Answer 60

**decreased**

Question 61

This patient with **morbid obesity has normocytic anemia with a low reticulocyte count,** raising strong suspicion for **anemia of ------.** Because ---- is t**riggered by long-standing elevations in serum inflammatory cytokines**, it is classically **associated with** underlying **rheumatologic disease, persistent infection, or malignancy.** However, it is also commonly caused by less obvious sources of inflammation such as **type 2 diabetes mellitus, congestive heart failure, severe traumatic injury, and morbid obesity.** The **major inflammatory cytokine** that drives ACD is -----

Answer 61

chronic disease (ACD) hepcidin

Question 62

**Hyponatremia** following **cerebral injury (eg, subarachnoid hemorrhage**) is commonly due to --------. Injury to the hypothalamus leads to **increased secretion of antidiuretic hormone**, which in turn leads to **water retention, low serum osmolality, and increased urinary sodium excretion**

Answer 62

the syndrome of inappropriate antidiuretic hormone secretion

Question 63

The **third heart sound (S3)** is a low-frequency sound occurring immediately after S2 that is commonly associated with **increased ----- volume.** S3 frequently occurs in the setting of **mitral regurgitation and systolic heart failure (eg, dilated cardiomyopathy).**

Answer 63

ventricular end-systolic

Question 64

Traumatic ---- can involve **puncture of either the chest wall (eg, penetrating chest trauma) or the lung** (eg, by fractured ribs), allowing air to enter the pleural space. Patients usually experience **chest pain and difficulty breathing.** physical examination reveals: **decreased breath sounds** and **decreased tactile fremitus on the affected side**. **hyperresonance to percussion &** **subcutaneous crepitus (ie, crackling during palpation).**

Answer 64

pneumothorax

Question 65

**Sicle cell pt**. The smear findings indicated by the arrow most likely reflect which of the following processes?

Answer 65

This patient's peripheral smear shows a **Howell-Jolly body,** a **dark-purple remnant of a red blood cell (RBC) nucleus** that is normally removed by the spleen. In patients with **asplenia**, which can be anatomic (eg, splenectomy) or functional (eg, **sickle cell disease [SCD]),** Howell-Jolly bodies are not removed from circulation and are therefore present on peripheral smear. This patient also has sickle-shaped RBCs and polychromasia (indicative of reticulocytosis) on peripheral smear, consistent with her underlying SCD.