Comprehensive Histology Study Guide: Cellular Anatomy and Physiology

General Overview of the Cell and Its Components

Cell biology and histology provide the foundational understanding of the smallest functional units of life. The cell is described as a complex entity composed of several specialized structures called organelles, which are organized within the cytoplasm or the nucleus. The hierarchical organization of biological life proceeds from cells to tissues, then to organs, and finally to systems or apparatuses. The internal content of the cell is broadly termed protoplasm. This is further divided into the karioplasm, which represents the contents of the nucleus, and the cytoplasm. The cytoplasm itself consists of the cytosol (an aqueous solution also known as the intracellular fluid) and various organelles.

Basic cellular functions include the synthesis of macromolecules for internal use or secretion, the generation of energy to power metabolic processes, and communication with other cells and the surrounding environment. The structural integrity of the cell is maintained by the cytoskeleton and various inclusions. Key components visible in cellular anatomy include microtubules, actin microfilaments, intermediate filaments, microvilli, centrosomes, the plasma membrane, lysosomes, smooth endoplasmic reticulum (SER), peroxisomes, mitochondria, cilia, flagella, secretory vesicles, the Golgi apparatus, chromatin, the nuclear envelope, the nucleolus, glycogen granules, the rough endoplasmic reticulum (RER), and ribosomes.

The Plasma Membrane and Glycocalyx

The plasma membrane, also known as the cellular membrane or plasmalema, serves as the primary boundary that limits the cell, acting as an interface between the cytoplasm and the external environment. Its functions are multifaceted, involving the maintenance of cellular structure and the control of selective permeability. It regulates intercellular interactions, recognizes antigens and foreign cells, and facilitates the transport of molecules. Additionally, it maintains the difference in potential between the intracellular and extracellular environments and transduces physical and chemical signals from both external and internal sources.

Structurally, the plasmalema is composed of a phospholipid bilayer and proteins. Each phospholipid molecule consists of a polar head made of glycerol and two non-polar fatty acid tails. The membrane also incorporates glycolipids, glycosphingolipids, and cholesterol. Specific regions known as lipid rafts (balsas lipídicas) exist to facilitate and improve intercellular communication. Integral or transmembrane proteins within the membrane contain both hydrophilic and hydrophobic amino acids; these proteins often form ion channels and function as transport proteins.

The glycocalyx, or cell coat, consists of carbohydrate chains attached to transmembrane proteins and phospholipid molecules. The primary function of the glycocalyx is to protect the cell from harmful proteins and physical or chemical injuries. It plays a significant role in intercellular recognition and adhesion, facilitates blood coagulation and the inflammatory response, and reduces friction between the blood and endothelial cells.

Ribosomes and the Endoplasmic Reticulum

Ribosomes are non-membranous organelles found either free in the cytosol or related to the membrane of the endoplasmic reticulum. They are composed of approximately $40\%$ proteins and $60\%$ ribosomal RNA (rRNA). Their primary function is the synthesis of all cellular proteins. Ribosomes are structured into two distinct parts: a small subunit and a large subunit.

The endoplasmic reticulum (RE) is the most extensive membranous organelle in the cell, comprising a system of interconnected tubules and vesicles. It is categorized into two types: rough (RER) and smooth (SER). The rough endoplasmic reticulum has its cytoplasmic surfaces coated with ribosomes and is involved in protein production. Integral proteins associated with the RER include docking proteins, ribosome receptor proteins, and pore proteins. Structural proteins that model the RE include reticulons, kinectins (cinectinas), and atlastins. The smooth endoplasmic reticulum lacks associated ribosomes and consists of a system of anastomosed tubules and flat vesicles. In skeletal muscle cells, the SER is specialized as the sarcoplasmic reticulum, which helps control muscle contraction.

The Golgi Apparatus and Lysosomes

The Golgi apparatus is formed by one or several stacked, flat, and slightly curved cisternae bound to a membrane. It exhibits polarity, with a "cis" face and a "trans" face. The cis face is convex and related to the RER, serving as the entry face for proteins. The trans face is concave and serves as the exit face. The primary functions of the Golgi apparatus include the synthesis of carbohydrates and the modification and sorting of proteins produced by the RER.

Lysosomes are membranous organelles that contain hydrolytic enzymes. Each lysosome contains at least $40$ different types of acid hydrolases, such as sulfatases, proteases, nucleases, lipases, and glycosidases. These organelles are formed from the trans face of the Golgi apparatus. They are responsible for intracellular digestion, degrading materials through their enzymes. This includes the degradation of old or damaged organelles to reuse their components (recycling), the destruction of bacteria and viruses, and the elimination of intracellular waste.

Mechanisms of Endocytosis and Transport

The transport of substances toward lysosomes involves several pathways, including the use of autophagosomes and autolysosomes. Endocytosis is a general term for processes by which the cell incorporates material. Pinocytosis involves the intake of liquids from the extracellular environment in small drops; it is an active process requiring adenosine triphosphate (ATP) and is non-selective. Phagocytosis is the process by which phagocytes, such as neutrophils and monocytes (macrophages), absorb large particles.

Endosomes are classified as early (located near the membrane) or late (located deeper in the cytoplasm). During pinocytosis, vesicles lose their clatrin coating and join early endosomes. For the total degradation of the contents of a pinocytic vesicle, the material must pass from the early endosome to the late endosome.

Peroxisomes, Proteasomes, and Mitochondria

Peroxisomes are spherical or oval organelles containing oxidative enzymes, including urate oxidase, catalase, and D-amino acid oxidase. Their function is to degrade uric acid, amino acids, purines, and both long-chain and very-long-chain fatty acids. Proteasomes are small organelles consisting of protein complexes assigned to the proteolysis of malformed, defective, or aged proteins that have entered a turnover cycle.

Mitochondria are flexible organelles that vary in size, number, and shape. They possess their own DNA and are the sites of oxidative phosphorylation and lipid synthesis. A mitochondrion has two membranes. The outer membrane contains porins, while the inner membrane is folded into cristae. The inner membrane is provided with cardiolipin, which makes it impermeable to ions, electrons, and protons.

Cytoplasmic Inclusions and the Cytoskeleton

Inclusions are non-living components of the cell. Glycogen is the storage form of glucose; deficiencies or issues with its metabolism lead to conditions like Von Gierke disease, myopathic McArdle syndrome, and Pompe disease. Pigments include hemoglobin, melanin, and lipofuscin. Lipids are stored as triglycerides and represent a highly efficient form of energy reserve. Crystals are found in Sertoli cells, interstitial cells, and macrophages.

The cytoskeleton is a complex mesh within the cytoplasm and nucleus responsible for structural support. It is composed of three main elements. Thin filaments (microfilaments) are approximately $7\,nm$ in diameter, formed by actin subunits that interact with myosin to induce movement. Intermediate filaments are $8-12\,nm$ in diameter and provide structural support, anchor the nucleus, and maintain the nuclear envelope. Microtubules are rigid, long, straight structures with a diameter of $25\,nm$. They are found in cilia and flagella, giving them mobility. Microtubules are formed by $13$ protofilaments composed of tubulin $\alpha$ and $\beta$ heterodimers, with functionality mediated by the centrosome and motor proteins like kinesin (cinesina) and dynein (dineína).

Centrioles, Centrosomes, and the Nucleus

Centrioles are cylindrical structures formed by $9$ triplets of microtubules. The centrosome consists of two centrioles and the pericentriolar matrix, which contains tubulin and pericentrin. The nucleus is the largest organelle and contains nearly all cellular DNA. It is typically spherical and centrally located, housing the nucleoplasm, nucleolus, and chromatin. It is separated from the cytoplasm by the nuclear envelope, a double membrane with an outer membrane, an inner membrane, and a perinuclear cisterna in between. The envelope is perforated by nuclear pores, which are controlled by nucleoporin complexes.

Chromatin is the complex of DNA and associated proteins. During cell division, it condenses to form chromosomes. The nucleolus is the site of ribosomal RNA (rRNA) synthesis and ribosome assembly. The total genetic information in the nucleus is the genome. In humans, somatic cells contain $46$ chromosomes grouped into $23$ pairs, consisting of $22$ pairs of autosomes and one pair of sex chromosomes ($XX$ or $XY$).

Chromatin States and Chromosome Structure

Chromatin exists in two states: heterochromatin and euchromatin. Heterochromatin is highly compact, transcriptionally inactive, stains darkly, and is located at the periphery of the nucleus. Euchromatin is less compact, transcriptionally active, stains lightly, and is located in the center of the nucleus. During mitosis and meiosis, chromatin fibers condense into chromosomes via proteins like Condensin I (found in the cytoplasm, dividing loops in metaphase) and Condensin II (found in the nucleolus, initiating loops during prophase).

A chromosome contains a compact DNA molecule, representing the maximum level of condensation, often seen in the "X" shape during metaphase. Chromatids are segments or arms of the chromosomes joined by the centromere. Telomeres can be short or long. Abnormalities in chromosome number are known as aneuploidies, such as Klinefelter syndrome.

Genetic Material: DNA and RNA

DNA (deoxyribonucleic acid) acts as the template for RNA transcription. It is a double helix consisting of purines (Adenine and Guanine) and pyrimidines (Cytosine and Thymine). Complementary base pairing occurs as $A-T$ and $G-C$. A gene is a specific segment of DNA that codes for a protein, a codon is a triplet of consecutive bases, and the genome is the complete set of genes. RNA (ribonucleic acid) is single-stranded (monocatenario) and contains ribose sugar; thymine is replaced by Uracil ($U$). Types of RNA include mRNA (messenger), rRNA (ribosomal), and tRNA (transfer).

Cell Division and Meiosis

Mitogens are substances that impel the cell to enter the cell cycle, such as erythropoietin or epidermal growth factor. Meiosis is the cell division that produces oocytes and spermatozoa. It involves a reduction in the number of chromosomes from diploid ($2n$) to haploid ($n$) and gene recombination. Meiosis I is the reductional division where homologous pairs of chromosomes are separated. Meiosis II is the equatorial division, which is similar to mitosis as it does not involve further DNA synthesis and results in $4$ haploid daughter cells. The phases include Prophase, Metaphase, Anaphase, and Telofase, followed by cytokinesis.

The Extracellular Matrix (ECM)

The extracellular matrix is a set of inert macromolecules produced and exported by cells. Its functions include modifying cell shape/function, influencing development, regulating survival and migration, directing mitotic activity, and resisting tension and compression. It is composed of the basic ground substance (sustancia fundamental) which includes glycosaminoglycans (e.g., hyaluronic acid, heparin, keratan sulfate, heparan sulfate, chondroitin sulfate, and dermatan sulfate) and proteoglycans (e.g., decorin, betaglycan, and aggrecan) that resist compression. Glycoproteins such as fibronectin, laminin, chondronectin, and osteonectin help cells bind to the matrix. Clinical correlations related to the ECM include necrotizing fasciitis and nephritic syndrome.

ECM fibers include collagen fibers formed by tropocollagen, which resist traction forces. Type I collagen is the most abundant, found in tendons and bones. Type II is found in cartilage, while Type III forms reticular fibers in the spleen and liver. Elastic fibers, produced by fibroblasts or smooth muscle cells, are composed of elastin, fibrillin $1$, fibulin $5$, and collagen Type VIII. The basement membrane (membrana basal) consists of the basal lamina (produced by epithelial cells, containing the lamina lucida and lamina densa) and the reticular lamina (produced by connective tissue cells).