Uworld Physio 4

Question 1

The duodenal brush border enzyme ——- activates trypsin from its inactive precursor, trypsinogen. Trypsin degrades complex polypeptides to dipeptides, tripeptides, and amino acids while activating other pancreatic enzymes.

Answer 1

enteropeptidase

Question 2

Enteropeptidase deficiency impairs both protein and fat absorption, leading to

Answer 2

diarrhea, failure to thrive, and hypoproteinemia

Question 3

Unilateral renal artery stenosis causes hypoperfusion and activation of the renin-angiotensin-aldosterone system. Angiotensin II causes arteriolar vasoconstriction and increases aldosterone and antidiuretic hormone synthesis. The resultant hypertension helps reduce the decline in glomerular filtration rate in the affected kidney, but causes a pressure natriuresis with increased —- excretion in the —— kidney.

Answer 3

increased sodium excretion in the unaffected

Question 4

Diffusion speed across a semipermeable membrane increases with —— molecular concentration gradients, larger/smaller membrane surface areas, and ——- solubility of the diffusing substance.

Diffusion speed decreases with increased membrane thickness, smaller pore size, higher molecular weights, and lower temperatures.

Answer 4

higher molecular concentration gradients

larger membrane surface areas

increased solubility of the diffusing substance.

Question 5

Point mutations in neurophysin II underlie most cases of hereditary hypothalamic ——–, a disorder resulting from insufficient ADH release into the systemic circulation.

Answer 5

diabetes insipidus

Question 6

Generalized hyperpigmentation is a manifestation of Addison’s disease, where a primary defect in adrenal cortisol production reduces feedback inhibition of anterior —— synthesis. As a result, —– cleavage products, including ACTH and melanocyte-stimulating hormone (MSH), are secreted in excess. High MSH levels cause increased melanin synthesis by melanocytes.

Answer 6

pituitary pro-opiomelanocortin (POMC)

Question 7

Neurophysins are carrier proteins for — & —- hormones produced within the paraventricular and supraoptic nuclei, respectively, and released from the posterior pituitary.

Answer 7

oxytocin and vasopressin

Question 8

Most patients with thyroid dysgenesis have hypothyroidism, with routine newborn screening findings of increased TSH and decreased thyroxine (T4) levels. However, newborns are typically asymptomatic for the first weeks due to the presence of ——-, which crosses the placenta in small amounts during gestation. The amount of neonatal T4 is still low compared to that in unaffected patients but is sufficient to initially prevent clinical manifestations of hypothyroidism.

Answer 8

maternal T4

Question 9

VIPomas are pancreatic islet cell tumors that hypersecrete vasoactive intestinal peptide (VIP), which increases intestinal chloride loss into the stool and causes excess losses of the accompanying water, sodium, and potassium.

VIP also inhibits —- secretion.

—— inhibits the secretion of VIP and is used to treat the symptoms of VIPoma

Answer 9

gastric acid

Somatostatin

Question 10

Excess —— secretion due to a pancreatic islet cell tumor called —oma can result in watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome (pancreatic cholera). — stimulates pancreatic bicarbonate and chloride secretion, and its binding to intestinal epithelial cells leads to adenylate cyclase activation and increased cyclic AMP production, causing sodium, chloride, and water secretion into the bowel (secretory watery diarrhea, often >3 L/day).

Answer 10

vasoactive intestinal peptide (VIP)

Question 11

CCK is produced by – cells of the proximal small bowel mucosa in response to fatty acids and amino acids.

Answer 11

I cells

Question 12

Motilin is produced by the duodenal mucosa and stimulates smooth muscle contraction in the upper GI tract. The antibiotic —– acts as an agonist at motilin receptors in the stomach and duodenum, contributing to the drug’s GI side effects.

Answer 12

erythromycin

Question 13

A glucagonoma is a pancreatic alpha cell tumor that hypersecretes glucagon and can cause —– and necrolytic migratory erythema of the skin.

Answer 13

secondary diabetes mellitus

Question 14

Pregnancy is a prothrombotic state due to increased or decreased

—— procoagulant factors (eg, fibrinogen),

——- anticoagulant factors (eg, protein S),

—– fibrinolysis.

Answer 14

increased procoagulant factors (eg, fibrinogen)

decreased anticoagulant factors (eg, protein S),

and reduced fibrinolysis.

Question 15

Pleural effusion in decompensated heart failure is primarily driven by backward transmission of pressure from the failing left ventricle to the pulmonary circulation, resulting in ——- pulmonary capillary hydrostatic pressure and an ——– rate of fluid inflow to the pleural space. ——- Vascular permeability &

—– vascular oncotic pressure.

Outflow through the parietal pleural lymphatics increases in response to the increased fluid inflow, but it is unable to keep up, resulting in development of pleural effusion.

Answer 15

increased pulmonary capillary hydrostatic pressure and an increased rate of fluid inflow to the pleural space.

Vascular permeability remains normal

normal vascular oncotic pressure

Question 16

In exogenous thyrotoxicosis, radioactive iodine uptake and serum thyroglobulin level are —, indicating suppression of endogenous thyroid metabolic activity. Serum T3 levels are often —–

Answer 16

low

elevated

Question 17

In the absence of ADH, the tubular fluid is most concentrated at the ——– and most dilute in the collecting ducts

Answer 17

junction between the descending and ascending limbs of the loop of Henle

Question 18

Subacute (granulomatous, de Quervain) thyroiditis presents with fever; a painful, tender goiter; and an elevated erythrocyte sedimentation rate. Patients initially develop hyperthyroidism due to the destruction of thyroid follicles and release of preformed thyroid hormone. TSH is —– due to feedback inhibition on the pituitary; as a result, thyroid metabolic activity and organification of iodine are decreased, and radioactive iodine uptake is —-

Answer 18

TSH is suppressed

radioactive iodine uptake is low

Question 19

Erythropoietin (EPO) is produced by peritubular fibroblast cells in the renal cortex in response to decreased renal oxygen delivery. EPO acts on erythrocyte precursors in the bone marrow to increase ——

Answer 19

red blood cell production/ progeniter differation

Question 20

Patients with chronic kidney disease often have damage to renal EPO-producing cells, which results in —– anemia.

Answer 20

normocytic

Question 21

Protoporphyrins (heme precursors) are elevated in patients with —— anemia. Treatment (eg, iron supplementation) leads to the conversion of protoporphyrins to heme, thereby reducing free protoporphyrin level

Answer 21

iron deficiency

Question 22

Warm autoimmune hemolytic anemia is characterized by antibodies against antigens on the red cell membrane that result in phagocytosis in the —— system (eg, spleen). Autoimmune hemolytic anemia is usually treated with immune-suppressing agents (eg, prednisone), which blunt antibody production and reduce red cell destruction

Answer 22

reticuloendothelial

Question 23

thyrotoxicosis due to the intake of liothyronine (exogenous T3) is associated with —- serum T3 and —- T4

Answer 23

high T3

low T4

Question 24

When exogenous thyrotoxicosis is due to levothyroxine or mixed T3/T4 supplements (eg, porcine thyroid extract), total and free thyroxine (T4) levels are —–;

T3 levels also are —–

Answer 24

elevated

Question 25

Because **TSH can promote growth of residual malignant cells following thyroidectomy**, patients with **thyroid cancer** at high risk of recurrence (eg, known metastasis) are often prescribed ------- doses that are higher than what is needed for simple replacemen

Answer 25

levothyroxine

Question 26

Key adaptive responses to **hypoxemia** include **hyperventilation** to increase blood oxygenation and **increased synthesis of ------** in erythrocytes (facilitating oxygen offloading into peripheral tissues).

Answer 26

**2,3-bisphosphoglycerate**

Question 27

**Inspiration** is driven by an increase in intrathoracic volume. This is mediated predominantly by **contraction of the diaphragm,** which is innervated by the **phrenic nerve** that originates from the C- to C- nerve rootlets

Answer 27

C3-C5

Question 28

The membrane is most permeable to potassium ions at which of the following points?

Answer 28

D **Depolarization results from massive influx of Na+ through voltage-gated Na+ channels. Repolarization occurs due to closure of voltage-gated Na**+ channels and o**pening of voltage-gated K+ channels.** **K+ ion** permeance is **highest during the repolarization** phase of the action potential.

Question 29

**Pleural fluid** normally enters the pleural space via filtration from the systemic circulation, primarily from the -**----- microvessels** of the **parietal pleura**, and **exits** the pleural space via stomata in the parietal pleura that drain into the **parietal ------**

Answer 29

intercostal parietal pleura lymphatics

Question 30

Duodenal **S-cells** secrete **secretin** in **response to increasing H+ concentrations.** Secretin increases pancreatic ---- secretion.

Answer 30

bicarbonate

Question 31

The **-----** content of pancreatic secretions **decreases** as the **bicarbonate content increases**, because --- and bicarbonate are exchanged for one another at the **apical surfaces** of pancreatic ductal cells.

Answer 31

**chloride**

Question 32

The **contractile** mechanism in **_skeletal muscle_** depends on proteins (---,----,----,-----) as well as **calcium ions.**

Answer 32

myosin II, actin, tropomyosin, and troponin

Question 33

**Calmodulin** and ------- are elements of the **contractile** mechanism in **_smooth muscle_**

Answer 33

myosin light-chain kinase

Question 34

**-------** is the **neurotransmitter** that initiates **muscle contraction** in response to **motor neuron stimulation**. ------- release from the motor neuron **opens post-synaptic ligand-gated ion channels,** resulting in **depolarization of the muscle cell**. Depolarization then causes release of **Ca2+ from the sarcoplasmic reticulum.**

Answer 34

**Acetylcholine**

Question 35

When ----- **binds troponin C,** **tropomyosin shifts to expose the actin binding sites** for myosin, allowing **contraction to occur**

Answer 35

Ca2+

Question 36

**_Gestational thrombocytopenia_** is common in the **third trimester** and is typically mild, asymptomatic, and not associated with other laboratory abnormalities. It occurs due to ------- and increased ------- of platelets in the placenta.

Answer 36

**hemodilution** (ie, maternal plasma volume expansion) and **increased sequestration/consumption of platelets in the placenta.**

Question 37

Patients with **_chronic kidney disease (CKD_**) often develop **symptomatic anemia (eg, fatigue, exertional dyspnea)** as the glomerular filtration rate declines. Most cases are due to the **inadequate secretion of -------**, a glycoprotein hormone produced by **_peritubular fibroblasts in the renal cortex_** in response to tissue **hypoxia** (as is seen with anemia). ---- acts on erythrocyte precursor cells (erythroid colony–forming unit cells) in the bone marrow to **stimulate red blood cell differentiation and survival**

Answer 37

**erythropoietin (EPO)**

Question 38

**Congenital goiter** in the setting of **hypothyroidism (↑ TSH, ↓ thyroxine)** can be caused by **transplacental passage of -------**, which **inhibit thyroid peroxidase** and are used to treat **maternal hyperthyroidism.**

Answer 38

**maternal antithyroid medications (eg, propylthiouracil)**

Question 39

**Propylthiouracil crosses the placenta**, **inhibiting production of T4**. Positive feedback caused by low T4 **leads to increased TSH**, which stimulates the thyroid and **causes diffuse gland enlargement**. TSH and T4 levels typically normalize after 1-2 weeks due to excretion of the maternally derived antithyroid medication. **After elimination of propylthiouracil, neonates with mothers who have Graves disease may then develop** transient ------- due to transplacental transfer of **TSH receptor–stimulating antibodies**, which can persist in the neonatal circulation for up to 3 months.

Answer 39

hyperthyroidism (↓ TSH, ↑ T4)

Question 41

**Excessive vitamin D** intake can lead to **hypercalcemia** and cause **mental status changes, muscle weakness, constipation, and polyuria/polydipsia**. Activated macrophages in ------- and other **granulomatous diseases** express **1-α-hydroxylase**, leading to excess production of 1,25-dihydroxyvitamin D and hypercalcemia.

Answer 41

sarcoidosis

Question 42

Normally, **25-hydroxyvitamin D** is converted to **1,25-dihydroxyvitamin D** (the active form) by ------ in the kidneys, a process **regulated by parathyroid hormone (PTH)**

Answer 42

1-α-hydroxylase

Question 43

**----- disease** (hepatolenticular degeneration) is characterized by **impaired incorporation of copper into ceruloplasmin** an**d defective excretion of excess copper into bile**. This leads to **elevated blood free copper levels** and deposition in the liver **(cirrhosis)** and **brain (motor abnormalities, psychiatric symptoms).**

Answer 43

**Wilson**

Question 44

**Airway resistance is high in the trachea** and **reaches a peak** in the -------, where total cross-sectional area is at a minimum. **Airway resistance then progressively decreases** as total cross-sectional area increases through the **smaller bronchioles, terminal bronchioles, and alveoli.**

Answer 44

medium-sized bronchi

Question 45

In the **presence of ADH**, the **collecting ducts contain the most concentrated fluid** in the nephron, while the ------ contains the **most dilute fluid.**

Answer 45

distal convoluted tubule

Question 46

Serum ---- levels are useful as an **early marker** for monitoring **abnormal phosphate metabolism** in patients with **_CKD._**

Answer 46

FGF23

Question 47

**Patients with chronic kidney disease (CKD)** can develop **hyperphosphatemia** due to decreased filtration of phosphate. ------ is **secreted in response to hyperphosphatemia and lowers plasma phosphate** by reducing intestinal absorption and renal reabsorption of phosphate. ---- levels are **useful as an early marker of abnormal phosphate metabolism in patients with CKD.**

Answer 47

Fibroblast growth factor 23 (FGF23)

Question 48

This patient's clinical presentation (**progressive dyspnea, fine crackles, clubbing, diffuse reticular opacities**) is consistent with ---- lung disease

Answer 48

interstitial

Question 49

**_Interstitial lung disease_** is associated with **decreased lung volumes** and **increased lung elastic recoil** caused by fibrotic interstitial tissue. The increased elastic recoil results in **increased ------** on the airways, leading to **increased expiratory flow rates** when corrected for the low lung volume.

Answer 49

**radial traction (outward pulling)**

Question 51

**Vascular calcifications** occur more commonly in patients with **_chronic kidney disease_** due to electrolyte abnormalities (eg, -----,------) and chronic inflammation (secondary to atherosclerosis and/or uremia). These changes promote calcification and suppress calcification inhibitors, which can result in extensive vascular calcifications

Answer 51

hyperphosphatemia, hypercalcemia

Question 52

**Hyperphosphatemia** (decreased filtration and excretion of phosphorus) and/or **hypercalcemia** (typically iatrogenic due to the administration of calcium products as phosphate binders) **promote calcification** by stimulating ------

Answer 52

osteogenic differentiation

Question 53

**_Sunlight exposure_** catalyzes conversion of ------- to ----- (vitamin D3) in the **skin**. Subsequent **25-hydroxylation in the liver** and **1-hydroxylation in the kidneys** produce 1,25-dihydroxyvitamin D, the active form. Inadequate exposure to sunlight can lead to vitamin D deficiency.

Answer 53

7-dehydrocholesterol to cholecalciferol (vitamin D3)

Question 54

**Patients with type 1 diabetes** **mellitus** are at **increased risk of hypoglycemia** because **exogenous insulin will continue to be absorbed from the injection site despite falling glucose levels.** Those with long-standing diabetes may also have **decreased ------ secretion** and therefore have an even greater risk of rapid hypoglycemia.

Answer 54

**decreased glucagon secretion**

Question 55

**Progressive hypoglycemia** prompts a ----- surge, which **increases hepatic glucose production** and triggers many of the characteristic hypoglycemic symptoms (eg, arousal, tremor)

Answer 55

catecholamine (eg, epinephrine)

Question 56

**Mutations in the potassium-ATP channel** causing **increased affinity for ATP** result in fewer open channels and **depolarization at lower glucose** concentrations. This c**auses continued secretion of insulin despite falling blood glucose levels**, leading to -----

Answer 56

congenital hypoglycemia

Question 57

**Mutations of the potassium-ATP channels** that **_decrease ATP affinity_** **prevent appropriate depolarization** in response to rising glucose levels, causing a **familial form of ------.** These patients can be treated successfully with **sulfonylureas**, which bind to KATP channels and cause closure independent of ATP.

Answer 57

**neonatal diabetes mellitus**

Question 58

**In pregnancy**, **----** is secreted by the corpus luteum and later by the placenta. Although prolactin secretion increases as pregnancy progresses, **high ------ levels inhibit lactation** by preventing binding of prolactin to receptors on alveolar cells in the breast.

Answer 58

**progesterone**

Question 59

In the **second and third trimesters**, **progesterone** is produced by the **placenta** and **suppresses ---- and ---** though action on the anterior pituitary

Answer 59

**suppresses FSH and LH**

Question 60

**Prolactin** is a **peptide hormone** that promotes **lactogenesis** (ie, maturation of breast alveolar cells) and **milk production**. It is released by the anterior pituitary gland due to **stimulation** by ------ hormone

Answer 60

thyrotropin-releasing hormone (TRH)

Question 61

**Creatinine**, a waste product generated by the breakdown of creatine in the muscles, is **used to estimate the glomerular filtration rate (GFR)**. Creatinine formation is dependent on **muscle mass and meat intake**; therefore, patients with **low ---- mass** or low intake **----** can have **significantly lower GFRs** for any given creatinine level (2 pts with same creatinine level but one has a lot lower GFR)

Answer 61

**low muscle mass (eg, elderly patient, those with amputations)** **(eg, low-protein vegetarian diet)**

Question 62

**Normal aging in men** is associated with a **slow decline in gonadal testosterone production**, a compensatory **rise in --**, and **rising serum levels of------.** Common, nonspecific symptoms include **decreased ejaculate volume**, **increased erectile latency and sexual refractory time**, and moderately **impaired erectile function.**

Answer 62

**rise in LH** **rising serum levels of sex hormone–binding globulin**

Question 63

**Pulse pressure** is the amount that arterial pressure increases above diastolic pressure during **left ventricular contraction**; it is **directly related to stroke volume** and **inversely related** to -----

Answer 63

aortic compliance

Question 64

**Systolic blood pressure** is the **summation** of **diastolic pressure** and --- pressure.

Answer 64

pulse

Question 65

**Age-related** ------- is the **primary driver of characteristic blood pressure changes** that occur in those **age \>65.** The **reduced aortic compliance** in the setting of **unchanged stroke volume** leads to **increased pulse pressure.**

Answer 65

stiffening of the aorta

Question 66

The **systolic hypertension** induced by **aortic stiffening** likely contributes to mild **-----** left ventricular **hypertrophy,** another common finding in **elderly individuals.**

Answer 66

**concentric**

Question 67

**Osteoclasts** originate from **hematopoietic progenitor cells**. **Macrophage colony-stimulating factor** and ------play an **_important role in osteoclast differentiation_**. **Paget's disease of bone** is characterized by **increased numbers of abnormal osteoclasts**, excessive **bone turnover** and **disorganized bone remodeling.**

Answer 67

receptor for activated nuclear factor kappa-B ligand **(RANK-L)**

Question 68

**Osteoblasts** are cells with a single nucleus that arise from **----- cells** found in the **periosteum and bone marrow.**

Answer 68

**mesenchymal stem cells**

Question 69

**osteoclasts** originate from the **mononuclear phagocytic cell lineage** and are ultimately formed when several precursor cells fuse to create a **--------**. Osteoclasts in **Paget's disease** are typically very large and **can have up to 100 nuclei**

Answer 69

multinucleated mature cell

Question 70

**Fibroblast growth factors (FGFs)** regulate **chondrogenesis and osteogenesis**. FGFs induce proliferation of **osteoblastic precursor cells** and anabolic function of **mature osteoblasts**. **Abnormalities in the FGF receptor** result in the congenital ------

Answer 70

short-limbed dwarfism known as **achondroplasia.**

Question 71

----- **stimulates appetite** and **promotes weight gain**. ----- and ----- act in the CNS to **decrease appetite.**

Answer 71

Ghrelin Leptin and insulin

Question 72

**_Caloric restriction_** leads to **increased ------ levels** along with **decreased ----- and ------ levels**, causing an **increase in appetite** that can make it **difficult to maintain weight loss.**

Answer 72

**increased ghrelin levels** **decreased insulin and leptin levels**

Question 73

**Overeating and weight gain** suppress ----- secretion and **increase secretion of leptin and insulin.**

Answer 73

ghrelin

Question 74

**Patent ductus arteriosus** results in **increased left ventricular preload** (due to increased pulmonary venous return to the left atrium) and **------- systemic vascular resistance** (due to the continuous **left-to-right shunt**). This combination of **higher preload and lower afterload** leads to an early **increase in left ventricular cardiac output.**

Answer 74

decreased systemic vascular resistance

Question 75

**Myocardial oxygen extraction exceeds that of any other tissue or organ**; therefore, the cardiac venous blood in the **------** is the **most deoxygenated blood in the body.**

Answer 75

coronary sinus

Question 76

**_Ventricular septal defect_** causes **left-to-right shunting** with **------ right ventricular pressure** and, if large, left-sided volume overload with **----- left ventricular and left atrial pressures.** Unchangged right atrium pressure. A **holosystolic murmur** is characteristic, and **failure to thrive** and signs of heart failure (eg, **poor feeding, diaphoresis) can occur.**

Answer 76

**increased**

Question 77

**_Advanced chronic kidney disease_** typically involves the accumulation of unmeasured acidic compounds in the blood; therefore, **anion gap metabolic -----** with **respiratory compensation** is expected.

Answer 77

**acidosis**

Question 78

------ is **produced by S cells** in the **duodenal mucosa** in response to stimulation by intraluminal acidity. ---- **_stimulates the release of bicarbonate-rich secretions_** from the exocrine pancreas, which is the major source of acid-neutralizing bicarbonate entering the duodenum.

Answer 78

Secretin

Question 79

**acute heart failure** can be treated with an infusion of **sodium nitroprusside.** Sodium nitroprusside is a short-acting agent that **causes balanced vasodilation** of the veins and arteries; as such, it ------ **left ventricular (LV) preload and afterload**, allowing for **maintenance of cardiac output (unchanged stroke volume)** at a lower LV pressure (decreased LV work). LV contractility is essentially unchanged.

Answer 79

decreases left ventricular (LV) preload and afterload

Question 80

During the normal cardiac cycle, **central aortic pressure is higher than right ventricular pressure** during systole and diastole. Consequently, an **intracardiac fistula between the aortic root and right ventricle** will most likely demonstrate a **left-to-right cardiac shunt** as blood **continuously flows** from the ---- to ----

Answer 80

aortic root (high pressure) to the right ventricle (low pressure).