Histology

Histology US Medical PG Question 1: A scientist is studying the anatomy and function of bone growth. He is able to create a cell line of osteocytes with a mutation that prevents the osteocytes from exchanging nutrients and waste products within neighboring lamellae. This mutation most likely affected which of the following cell structures?

• A. Dynein
• B. Gap junctions (Correct Answer)
• C. Endoplasmic reticulum
• D. Plasma membrane
• E. Kinesin

Histology Explanation: ***Gap junctions*** - **Gap junctions** are specialized intercellular connections that permit direct communication and exchange of small molecules and ions between adjacent cells. - In osteocytes, **gap junctions** located in the **canaliculi** are crucial for the exchange of nutrients, waste, and signaling molecules within and between lamellae, allowing for synchronous activity and maintaining bone health. - These connexin-based channels physically connect the cytoplasm of neighboring osteocytes embedded in bone matrix. *Dynein* - **Dynein** is a motor protein involved in intracellular transport towards the minus end of **microtubules**, playing a role in moving organelles and vesicles. - It is not directly responsible for the intercellular exchange of nutrients and waste products between cells. *Endoplasmic reticulum* - The **endoplasmic reticulum** is an organelle involved in protein synthesis and lipid metabolism, playing a critical role in cellular function. - It does not directly mediate the exchange of nutrients and waste products between adjacent cells. *Plasma membrane* - While **gap junctions** are embedded within the **plasma membrane**, the membrane itself does not facilitate direct cytoplasmic continuity between cells. - The question specifically refers to structures that enable direct cell-to-cell exchange; the mutation affects the gap junction channels themselves (connexins), not the general plasma membrane structure. - Without functional gap junctions, the plasma membrane alone cannot support the intercellular communication required for osteocyte networks. *Kinesin* - **Kinesin** is a motor protein that moves cargo along **microtubules** towards the plus end, involved in fundamental cellular processes like cell division and organelle transport. - It is not involved in direct intercellular communication for nutrient and waste exchange but rather internal cellular trafficking.

Histology US Medical PG Question 2: An investigator is studying the function of the endoplasmic reticulum in genetically modified lymphocytes. A gene is removed that facilitates the binding of ribosomes to the endoplasmic reticulum. Which of the following processes is most likely to be impaired as a result of this genetic modification?

• A. Production of secretory proteins (Correct Answer)
• B. Neutralization of toxins
• C. Ubiquitination of proteins
• D. α-Oxidation of fatty acids
• E. Synthesis of ketone bodies

Histology Explanation: ***Production of secretory proteins*** - Ribosomes bound to the **rough endoplasmic reticulum (RER)** are responsible for synthesizing proteins destined for secretion, insertion into membranes, or delivery to organelles like lysosomes. - If ribosomes cannot bind to the ER, these proteins will be synthesized in the **cytosol** and lack the proper signals and processing for their intended destination and function. *Neutralization of toxins* - The **smooth endoplasmic reticulum (SER)**, not the RER, is primarily involved in **detoxification** processes, particularly drug metabolism and neutralization of toxins. - This function relies on enzymes embedded within the SER membrane and is largely independent of ribosome binding. *Ubiquitination of proteins* - **Ubiquitination** is a post-translational modification that tags proteins for degradation by the **proteasome** or for trafficking to specific cellular compartments. - This process occurs primarily in the **cytosol** and does not directly rely on ribosome binding to the ER for protein synthesis. *α-Oxidation of fatty acids* - **α-oxidation of fatty acids** is a metabolic pathway that occurs primarily in the **peroxisomes**. - It is distinct from protein synthesis on the ER and would not be directly impacted by the inability of ribosomes to bind to the ER. *Synthesis of ketone bodies* - The **synthesis of ketone bodies** (ketogenesis) primarily occurs in the **mitochondria** of liver cells. - This metabolic pathway is not directly dependent on ribosome binding to the endoplasmic reticulum for its function.

Histology US Medical PG Question 3: A 65-year-old man with a 40-pack-year smoking history presents with hemoptysis and a persistent cough. Chest CT shows a 3.5 cm centrally located mass in the right main bronchus. Positron emission tomography confirms a malignant nodule. Bronchoscopy with transbronchial biopsy is performed and a specimen sample of the nodule is sent for frozen section analysis. The tissue sample is most likely to show which of the following tumor types?

• A. Carcinoid tumor
• B. Metastasis of colorectal cancer
• C. Small cell lung carcinoma
• D. Large cell carcinoma
• E. Squamous cell carcinoma (Correct Answer)

Histology Explanation: ***Squamous cell carcinoma*** - This is the most likely diagnosis given the **central location** in the main bronchus, **heavy smoking history**, and presentation with **hemoptysis**. - **Squamous cell carcinoma** accounts for 25-30% of lung cancers and characteristically arises in **central/proximal airways**, making it readily accessible by **bronchoscopy**. - Histologically, it shows **keratin pearls** and **intercellular bridges** on biopsy. - The **central endobronchial location** and ability to obtain tissue via transbronchial biopsy strongly favor squamous cell over peripheral tumors. *Carcinoid tumor* - **Carcinoid tumors** are **neuroendocrine tumors** that can present as central endobronchial masses and cause hemoptysis. - However, they are typically **slow-growing** with more indolent presentation, and PET scans show **variable uptake** (often less intense than aggressive carcinomas). - They represent only **1-2% of lung tumors** and occur more commonly in **younger, non-smoking patients**. *Metastasis of colorectal cancer* - While lung is a common site for **colorectal metastases**, these typically present as **multiple peripheral nodules** rather than a solitary central endobronchial mass. - The clinical presentation strongly suggests **primary lung cancer** rather than metastatic disease. - Without history of colorectal cancer, this is unlikely. *Small cell lung carcinoma* - **Small cell lung carcinoma** (SCLC) represents 15% of lung cancers and typically presents as a **large central mass** with early mediastinal involvement. - However, SCLC is usually **too extensive at presentation** for transbronchial biopsy alone and often requires mediastinoscopy or CT-guided biopsy. - Histology shows **small cells with scant cytoplasm**, **salt-and-pepper chromatin**, and **oat-cell morphology**. - While possible, the single accessible endobronchial mass is more characteristic of squamous cell. *Large cell carcinoma* - **Large cell carcinoma** is a **diagnosis of exclusion** made when tumors lack features of adenocarcinoma, squamous cell, or small cell differentiation. - It typically presents as **large peripheral masses** rather than central endobronchial lesions. - It represents only **10% of lung cancers** and is less common than squamous cell carcinoma in this clinical scenario.

Histology US Medical PG Question 4: An investigator is examining tissue samples from various muscle tissue throughout the body. She notices that biopsies collected from a specific site have a high concentration of sarcoplasmic reticulum, mitochondria, and myoglobin; they also stain poorly for ATPase. Additionally, the cell surface membranes of the myocytes in the specimen lack voltage-gated calcium channels. These myocytes are found in the greatest concentration at which of the following sites?

• A. Ventricular myocardium
• B. Tunica media
• C. Lateral rectus muscle
• D. Glandular myoepithelium
• E. Semispinalis muscle (Correct Answer)

Histology Explanation: ***Semispinalis muscle*** - The described characteristics—**high concentration of sarcoplasmic reticulum, mitochondria, and myoglobin** with **poor ATPase staining**—are hallmarks of **Type I (slow-twitch oxidative) skeletal muscle fibers**. - Postural muscles like the **semispinalis** (part of the erector spinae group) are predominantly composed of Type I fibers adapted for sustained, aerobic contraction to maintain posture. - These fibers appear **red** due to high myoglobin content, have abundant mitochondria for aerobic metabolism, and stain **poorly for ATPase** (distinguishing them from Type II fast-twitch fibers). - While all skeletal muscle does possess voltage-gated calcium channels for excitation-contraction coupling, the overall profile best matches slow-twitch postural muscles. *Ventricular myocardium* - While cardiac muscle has high mitochondria, myoglobin, and sarcoplasmic reticulum, it **does possess L-type voltage-gated calcium channels** on the sarcolemma, which are essential for cardiac excitation-contraction coupling. - Cardiac muscle relies on **both** extracellular Ca²⁺ influx through these channels and calcium-induced calcium release from the SR. - Cardiac muscle typically stains **strongly for ATPase**, not poorly. *Tunica media* - Composed of **vascular smooth muscle** with poorly developed sarcoplasmic reticulum and relatively few mitochondria compared to skeletal or cardiac muscle. - Smooth muscle relies heavily on **extracellular calcium influx** and the calmodulin pathway for contraction. - Not characterized by high myoglobin content. *Lateral rectus muscle* - This extraocular muscle contains predominantly **Type IIb fast-twitch glycolytic fibers** adapted for rapid, precise eye movements. - These fibers have **low myoglobin** (white muscle), fewer mitochondria, and stain **strongly for ATPase**. - Opposite profile from the described tissue. *Glandular myoepithelium* - Myoepithelial cells are specialized contractile cells in secretory glands with minimal sarcoplasmic reticulum and mitochondria. - Function is brief contraction for secretion expulsion, not sustained aerobic work. - Do not exhibit the high oxidative capacity described.

Histology US Medical PG Question 5: An 18-month-old boy of Ashkenazi-Jewish descent presents with loss of developmental milestones. On ocular exam, a cherry-red macular spot is observed. No hepatomegaly is observed on physical exam. Microscopic exam shows lysosomes with onion-skin appearance. What is the most likely underlying biochemical abnormality?

• A. Accumulation of ceramide trihexoside
• B. Accumulation of glucocerebroside
• C. Accumulation of galactocerebroside
• D. Accumulation of sphingomyelin
• E. Accumulation of GM2 ganglioside (Correct Answer)

Histology Explanation: ***Accumulation of GM2 ganglioside*** - This constellation of symptoms—**loss of developmental milestones**, **cherry-red macular spot**, absence of hepatomegaly, and **lysosomes with onion-skin appearance** in an individual of **Ashkenazi-Jewish descent**—is classic for **Tay-Sachs disease**. - **Tay-Sachs disease** is caused by a deficiency of **hexosaminidase A**, leading to the accumulation of **GM2 ganglioside** in neuronal lysosomes. *Accumulation of ceramide trihexoside* - This refers to **Fabry disease**, which is an **X-linked disorder** presenting in adolescence or adulthood with acroparesthesias, angiokeratomas, and renal/cardiac complications. - While it involves a lysosomal storage, its clinical presentation and the absence of a cherry-red spot differentiate it from the case described. *Accumulation of glucocerebroside* - This is characteristic of **Gaucher disease**, which is caused by a deficiency in **glucocerebrosidase**. - Key features include **hepatosplenomegaly**, bone pain, and pancytopenia, which are not consistent with the patient's presentation. *Accumulation of galactocerebroside* - This describes **Krabbe disease**, a **globoid cell leukodystrophy** caused by a deficiency in galactocerebrosidase. - Krabbe disease primarily affects the **myelin sheath** in the nervous system, leading to neurological degeneration but typically does not present with a cherry-red macular spot. *Accumulation of sphingomyelin* - This is the hallmark of **Niemann-Pick disease**, caused by **sphingomyelinase deficiency**. - While Niemann-Pick disease also presents with a **cherry-red macular spot** and neurodegeneration, it is classically associated with **hepatosplenomegaly**, which is explicitly stated to be absent in this patient.

Histology US Medical PG Question 6: In large neurons the nucleus can be found a large distance away from the terminal end of its axon. The body has a complex system of intracellular transporters that are able to carry essential proteins from the nucleus to the distal edge of the cell and back. Which of the following proteins are essential for this function?

• A. Kinesin, Troponin
• B. Myosin, Kinesin
• C. Actin, Dynein
• D. Dynein, Kinesin (Correct Answer)
• E. Glucose, Actin

Histology Explanation: ***Dynein, Kinesin*** - **Kinesin** is primarily responsible for **anterograde transport** (from the cell body to the axon terminal) along microtubules, carrying vesicles and organelles. - **Dynein** handles **retrograde transport** (from the axon terminal back to the cell body), essential for recycling components and signaling. *Kinesin, Troponin* - While **Kinesin** is involved in axonal transport, **Troponin** is a protein found in muscle tissue that regulates muscle contraction, not intracellular transport in neurons. - Troponin binds **calcium ions** and influences the interaction between actin and myosin. *Myosin, Kinesin* - **Kinesin** is involved in microtubule-based transport, but **Myosin** is primarily associated with **actin filaments** for muscle contraction and intracellular movement, not long-distance axonal transport. - Myosin functions as a **motor protein** that converts chemical energy in ATP into mechanical force. *Actin, Dynein* - **Dynein** is crucial for retrograde axonal transport, but **Actin** is a structural protein forming microfilaments that are involved in cell shape, motility, and some short-distance transport, not the major long-distance axonal transport mechanism. - Actin filaments serve as tracks for **myosin motors**, primarily in the cell cortex. *Glucose, Actin* - **Glucose** is a sugar molecule, the primary energy source for cells, and not a transport protein. - **Actin** forms microfilaments for cell structure and short-range movement, not long-distance axonal transport as described.

Histology US Medical PG Question 7: Steroid hormone synthesis, lipid synthesis, and chemical detoxification are activities of which of the following?

• A. Peroxisomes
• B. Nucleolus
• C. Rough Endoplasmic Reticulum
• D. Smooth Endoplasmic Reticulum (Correct Answer)
• E. Golgi bodies

Histology Explanation: ***Smooth Endoplasmic Reticulum*** - The **smooth endoplasmic reticulum (SER)** is rich in enzymes that catalyze the synthesis of **lipids**, including steroid hormones, and is crucial for the detoxification of drugs and poisons, particularly in liver cells. - Its tubular structure, devoid of ribosomes, differentiates its functions from the rough ER, focusing on metabolic processes like **calcium ion storage** and carbohydrate metabolism. *Peroxisomes* - Peroxisomes are primarily involved in the breakdown of **fatty acids** and amino acids, producing hydrogen peroxide as a byproduct. - They also play a role in detoxification but are not the primary site for steroid hormone or general lipid synthesis. *Nucleolus* - The **nucleolus** is a dense structure within the nucleus responsible for synthesizing **ribosomal RNA (rRNA)** and assembling ribosomes. - It has no direct role in steroid hormone synthesis, lipid metabolism, or chemical detoxification. *Rough Endoplasmic Reticulum* - The **rough endoplasmic reticulum (RER)** is studded with **ribosomes** and is primarily involved in the synthesis and modification of **proteins** destined for secretion or insertion into membranes. - While it's part of the endomembrane system, it does not directly perform lipid synthesis or chemical detoxification as its main functions. *Golgi bodies* - **Golgi bodies (or Golgi apparatus)** are responsible for modifying, sorting, and packaging **proteins and lipids** synthesized in the ER into vesicles for secretion or delivery to other organelles. - They do not perform the initial synthesis of steroid hormones or lipids, nor are they the primary site for chemical detoxification.

Histology US Medical PG Question 8: An investigator is studying human genetics and cell division. A molecule is used to inhibit the exchange of genetic material between homologous chromosomes. Which of the following phases of the cell cycle does the molecule target?

• A. Prophase II
• B. Prophase I (Correct Answer)
• C. Metaphase II
• D. Telophase I
• E. Anaphase I

Histology Explanation: ***Prophase I*** - **Crossing over** (genetic recombination) occurs specifically during **Prophase I** of meiosis, particularly during the pachytene stage - During this phase, homologous chromosomes pair up (synapsis) and exchange genetic material through recombination - Inhibiting this exchange means targeting the phase where this critical genetic recombination takes place *Prophase II* - Prophase II is a stage in meiosis II where chromosomes condense again after a brief interkinesis - **Crossing over does not occur** in Prophase II - genetic recombination has already been completed in Prophase I - Homologous chromosomes are no longer paired at this stage *Metaphase II* - During Metaphase II, individual chromosomes (not homologous pairs) align along the metaphase plate - There is **no exchange of genetic material** between homologous chromosomes at this stage - This phase prepares for the separation of sister chromatids *Telophase I* - Telophase I involves decondensation of chromosomes and reformation of nuclear envelopes around the separated homologous chromosomes - This marks the end of meiosis I, **after** genetic exchange has already occurred in Prophase I - No crossing over occurs during this phase *Anaphase I* - In Anaphase I, **homologous chromosomes separate** and move to opposite poles of the cell - This phase is characterized by segregation of chromosomes, **not genetic exchange** - Crossing over has already been completed by this stage

Histology US Medical PG Question 9: An investigator is conducting a study to document the histological changes in the respiratory tree of a chronic smoker. He obtains multiple biopsy samples from the respiratory system of a previously healthy 28-year-old man. Histopathological examination of one sample shows simple cuboidal cells with a surrounding layer of smooth muscle. Chondrocytes and goblet cells are absent. This specimen was most likely obtained from which of the following parts of the respiratory system?

• A. Terminal bronchiole (Correct Answer)
• B. Alveolar sac
• C. Main stem bronchus
• D. Bronchiole
• E. Respiratory bronchiole

Histology Explanation: ***Terminal bronchiole*** - Terminal bronchioles are lined by **simple cuboidal epithelium** and contain surrounding **smooth muscle** but lack cartilage (chondrocytes) and goblet cells, matching the histological description. - They represent the most distal purely conducting airways before respiratory bronchioles, where gas exchange begins. *Alveolar sac* - Alveolar sacs are primarily composed of **Type I and Type II pneumocytes** for gas exchange, and would not have a prominent smooth muscle layer or cuboidal cells in this described pattern. - They are the terminal structures of the respiratory tree where gas exchange occurs, defined by very thin walls lacking cartilage and goblet cells. *Main stem bronchus* - The main stem bronchi are characterized by **pseudostratified ciliated columnar epithelium** with abundant **goblet cells** and contain **hyaline cartilage** (chondrocytes) in their walls. - The presence of goblet cells and cartilage (chondrocytes) makes this option inconsistent with the given histological findings. *Bronchiole* - Bronchioles are generally lined by **ciliated columnar to cuboidal epithelium** with scattered goblet cells in larger ones, and they possess smooth muscle but lack cartilage. - While they share some features with terminal bronchioles, the presence of goblet cells (even if sparse) distinguishes bronchioles from terminal bronchioles. *Respiratory bronchiole* - Respiratory bronchioles are distinguished by their walls having occasional **alveoli**, indicating the beginning of gas exchange. Their epithelium is cuboidal. - They would not be described as having a "surrounding layer of smooth muscle" in isolation as clearly as a terminal bronchiole, and the presence of alveoli would be a key distinguishing feature.

Histology US Medical PG Question 10: A 38-year-old man comes to the physician because of a 6-month history of chest discomfort and progressive dyspnea. He cannot do daily chores without feeling out of breath. He was diagnosed in childhood with a milder X-linked dystrophinopathy that has caused progressive proximal muscle weakness and gait abnormalities over the years. Physical examination shows a waddling gait and weak patellar reflexes. Cardiovascular examination shows a holosystolic murmur, displaced point of maximal impulse, and bilateral pitting edema of the ankles. Laboratory studies show elevated levels of brain natriuretic peptide. Which of the following is the most likely underlying cause of this patient's muscle weakness?

• A. Increased number of CTG repeats in the DMPK gene
• B. Interruption of microtubule depolymerization through stabilization of GDP-tubulin
• C. Impaired connection of cytoskeletal actin filaments to membrane-bound dystroglycan (Correct Answer)
• D. Cell–mediated cytotoxicity against skeletal muscle antigens in the endomysium
• E. Defective lysine-hydroxylysine crosslinking of tropocollagen

Histology Explanation: ***Impaired connection of cytoskeletal actin filaments to membrane-bound dystroglycan*** - The description of a **milder X-linked dystrophinopathy** with progressive muscle weakness and gait abnormalities, coupled with cardiac manifestations like a **holosystolic murmur** and elevated **BNP**, is characteristic of a **dystrophinopathy**, such as **Becker muscular dystrophy**. - **Dystrophin** is a critical protein that links the **cytoskeletal actin filaments** to the **dystroglycan complex** at the sarcolemma, providing mechanical stability to muscle fibers. Impaired connection leads to muscle fragility and degeneration. *Increased number of CTG repeats in the DMPK gene* - This describes **myotonic dystrophy type 1**, which is an autosomal dominant condition, not X-linked. - While it causes muscle weakness, it is also associated with **myotonia**, testicular atrophy, and cataracts, which are not mentioned. *Interruption of microtubule depolymerization through stabilization of GDP-tubulin* - This mechanism is associated with **chemotherapeutic agents** like taxanes (e.g., paclitaxel, docetaxel), which interfere with cell division. - It does not explain a genetic, progressive muscle weakness disorder. *Cell–mediated cytotoxicity against skeletal muscle antigens in the endomysium* - This describes the pathophysiology of **polymyositis**, an **inflammatory myopathy**. - Polymyositis is an autoimmune condition and does not typically present as an X-linked inherited disorder diagnosed in childhood. *Defective lysine-hydroxylysine crosslinking of tropocollagen* - This mechanism is characteristic of disorders affecting **collagen synthesis** and cross-linking, such as **Ehlers-Danlos syndrome**. - These conditions primarily affect connective tissue, leading to joint hypermobility, skin hyperextensibility, and tissue fragility, not primarily progressive muscle weakness due to dystrophin deficiency.

Histology Flashcard 1 of 10

Question: What cellular structure are mucus-secreting goblet cells (small intestine) and antibody-secreting plasma cells rich in? _____

Answer: Rough endoplasmic reticulum

Histology Flashcard 2 of 10

Question: The base of a cilium below the cell membrane, called the _____, consists of 9 microtubule triplets with no central microtubules

Answer: basal body

Histology Flashcard 3 of 10

Question: What type of filament are cytokeratin and desmin?_____

Answer: Intermediate filaments

Histology Flashcard 4 of 10

Question: Which type of filament is predominantly involved in maintainence of cell structure? _____

Answer: Intermediate filaments (e.g. desmin, cytokeratin)

Histology Flashcard 5 of 10

Question: What form of chromatin appears lighter on EM? _____

Answer: Euchromatin

Histology Flashcard 6 of 10

Question: Langerhans cells are specialized _____ cells predominantly found in skin

Answer: dendritic

Histology Flashcard 7 of 10

Question: dermis

Answer: mesoderm

Histology Flashcard 8 of 10

Question: What organelles are stained with Nissl substance?

Answer: RER

Histology Flashcard 9 of 10

Question: What type of cytoskeletal element is most associated with cell structure?

Answer: intermediate filaments

Histology Flashcard 10 of 10

Question: Which layer of the epidermis is the regenerative (stem cell) layer? _____

Answer: Stratum basalis

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