Lecture #1

1. Lecture #1 INFO 590: Fundamentals of Clinical Care for Health Informaticians Body, Cell, Tissue and Membranes kharrazi@iupui.edu http://www.info590.com

2. Organization and General Plan of the Body Levels of Organization Metabolism and Homeostasis Terminology and General Plan of the Body Cells Cell Structure Cellular Transport Mechanisms The Genetic Code and Protein Synthesis Cell Division Tissues and Membranes Epithelial Tissue Connective Tissue Muscle Tissue Nerve Tissue Membranes Lecture in a Nutshell

3. Organization and General Plan of the Body

4. Levels of Organization Chemicals Cells Tissues Organs Organ Systems Metabolism and Homeostasis Terminology and General Plan of the Body Body Parts and Areas Terms of Location and Position Body Cavities and Their Membranes Planes and Sections Areas of the Abdomen Section Topics

5. Introduction • The human body is a precisely structured container of chemical reactions. • Anatomy is the study of body structure, which includes size, shape, composition, and perhaps even coloration (e.g., Iron on Hb) • Physiology is the study of how the body functions (e.g., Iron transfer O2) • Pathophysiology is the study of disorders of functioning, and a knowledge of normal physiology makes such disorders easier to understand (e.g., iron deficiency anemia)

6. Levels of Organization • Chemicals:Inorganic chemicals are usually simple molecules made of one or two elements other than carbon. Examples of inorganic chemicals are water (H2O); oxygen (O2); carbon dioxide (CO2); and minerals such as iron (Fe), calcium (Ca), and sodium (Na). Organic chemicals are often very complex and always contain the elements carbon and hydrogen (carbohydrates, fats, proteins, and nucleic acids). • Cells: The smallest living units of structure and function are cells. There are many different types of human cells, though they all have certain similarities. • Tissues: Epithelial tissues cover or line body surfaces; some are capable of producing secretions with specific functions. Connective tissues connect and support parts of the body; some transport or store materials. Muscle tissues specialized for contraction, which brings about movement. Nerve tissue specialized to generate and transmit electrochemical impulses that regulate body functions. • Organand Organ System: An organ is a group of tissues precisely arranged so as to accomplish specific functions. An organ system is a group of organs that all contribute to a particular function.

7. Level of Organization cont. Levels of structural organization of the human body, depicted from the simplest (chemical) to the most complex (organism). The organ system shown here is the urinary system.

8. Level of Organization cont. Highlighted organs will be reviewed in this course. The Organ Systems

9. Level of Organization cont.

10. Metabolism and Homeostasis • Metabolism: is a collective noun; it is all of the chemical reactions and physical processes that take place within the body. • Metabolism comes from a Greek word meaning “change”. Human body change in a visible (walking), microscopic (skin epidermis) and submicroscopic way (protein construction). • Metabolic Rate: is most often used to mean the speed at which the body produces energy and heat, or, put another way, energy production per unit of time, such as 24 hours. • Homeostasis: means good and healthy person, and reflects the ability of the body to maintain a relatively stable metabolism and to function normally despite many constant changes  body will create negative or positive feedback mechanisms to compensate for any changes. • Negative feedbacks: Thyroid gland and using energy; Sweating and excessive heat; Heart rate and blood pressure regulation. • Positive feedbacks: Oxytocin in childbirth; Blood clotting; Inflamation  needs an event to stop it (child is born, killing the germ…)

11. Metabolism and Homeostasis cont. Feedback mechanisms: (A) The negative feedback mechanism of regulation of metabolic rate by thyroxine. (B) The positive feedback mechanism triggered by a fever.

12. Terminology and General Plan of Body • Body Parts and Areas

13. Terminology cont. • Body parts and areas. The body is shown in anatomic position. • Anterior view. • (B) Posterior view. • Compare with the last table.

14. Terminology cont. The location and positions

15. Terminology cont. • Body Cavities: • Dorsal Cavity: The dorsal cavity contains the central nervous system, and consists of the cranial cavity and the vertebral or spinal cavity. The dorsal cavity is a continuous one; that is, no wall or boundary separates its subdivisions. The membranes that line these cavities and cover the brain and spinal cord are called the meninge. • Ventral Cavity: The ventral cavity consists of two compartments, the thoracic cavity(pleural and pericardial membranes) and the abdominal cavity (peritoneum), which are separated by the diaphragm.

16. Terminology cont. • Planes and sections of the body. • (B) Cross-section and longitudinal section of the small intestine.

17. Terminology cont. Transverse section through the upper abdomen

18. Terminology cont. Areas of the abdomen. (A) Four quadrants - a transverse plane and a midsagittal plane that cross at the umbilicus. (B) Nine regions.

19. Cells

20. Cell Structure Cell Membrane Nucleus Cytoplasm and Cell Organelles Cellular Transport Mechanisms Diffusion Osmosis Facilitated Diffusion Active Transport Filtration Phagocytosis and Pinocytosis The Genetic Code and Protein Synthesis DNA and the Genetic Code RNA and Protein Synthesis Cell Division Mitosis Meiosis Section Topics

21. Cell Structure • Cells are the smallest living subunits of a multicellular organism such as a human being. Microorganisms, such as amoebas and bacteria, are single cells that function independently. Human cells, however, must work together and function interdependently. Homeostasis depends upon the contributions of all of the different kinds of cells. • Cells are in the dimension of microns (micrometer) except from the human ovum (egg cell) that is around 1 mm and can be seen by unaided eyes. Some nerve cells are quite long (~60 cm) but still in microns. • With respect to shape, human cells vary greatly. Some are round or spherical, others rectangular, still others irregular. • Despite their many differences, human cells have several similar structural features: a cell membrane, a nucleus, and cytoplasm and cell organelles. Red blood cells have no nuclei when mature. • Cell (Plasma) Membrane: is made of phospholipids, cholesterol, and proteins. The phospholipids are diglycerides, and form a bilayer, or double layer, which makes up most of the membrane. Proteins form channels or pores, act as transporters, are antigens (when combines with oligosaccharides), or are receptors for hormones  selectively permeable.

22. Cell Structure cont. The cell (plasma) membrane depicting the types of molecules present.

23. Cell Structure cont. • Nucleus: The nucleus is within the cytoplasm and is bounded by a double-layered nuclear membrane with many pores. It contains one or more nucleoli and the chromosomes of the cell.A nucleolus is a small sphere made of DNA, RNA, and protein. The nucleoli form a type of RNA called ribosomal RNA, which becomes part of ribosomes (a cell organelle) and is involved in protein synthesis.The 46 chromosomes of a human cell are usually not visible; they are long threads called chromatin. Before a cell divides, however, the chromatin coils extensively into visible chromosomes. Chromosomes are made of DNA and protein.Only a small number of genes (a gene is the genetic code for one protein) are actually active  cells are different. • Cytoplasm: is a watery solution of minerals, gases, organic molecules, and cell organelles that is found between the cell membrane and the nucleus. Cytosol is the water portion of cytoplasm, and many chemical reactions take place within it.

24. Cell Structure cont. Generalized human cell depicting the structural components

25. Cell Structure cont. Function of Cell Organelles

26. Cell Transport Cellular Transport Mechanisms

27. Cell Transport cont. Cellular transport mechanisms. (A) Diffusion in an alveolus in the lung. (B) Osmosis in the small intestine. (C) Facilitated diffusion in a muscle cell. (D) Active transport in a muscle cell. (E) Filtration in a capillary. (F) Phagocytosis by a white blood cell. (G) Pinocytosis by a cell of the kidney tubules.

28. Cell Transport cont. Isotonic a solution with the same salt concentration as in cells. The blood plasma is isotonic to red blood cells. Hypotonic a solution with a lower salt concentration than in cells. Distilled water (0% salt) is hypotonic to human cells. Hypertonic a solution with a higher salt concentration than in cells. Red blood cells in different solutions and the effect of osmosis in each.

29. Genetic Code and Protein Synthesis Protein Synthesis

30. Gen Code and Pro Synthesis cont. If the this cycle has a problem  genetic or hereditary disease (e.g., Sickle Cell Anemia) Normal Cycle (Schematic): Transcription Protein synthesis. The mRNA is formed as a copy of a portion of the DNA in the nucleus of a cell. In the cytoplasm, the mRNA becomes attached to ribosomes. Translation

31. Gen Code and Pro Synthesis cont. • In the early 1980s, methods for DNA sequencing became widely available, and produced an exponential growth in molecular sequence data. • From the mid-1990s onwards, genetic sequence data for the whole genome of organisms were amassed. Completely sequenced genomes were available by 2003 for more than 100 organisms (e.g. Human Genome Project). • Databases such as GenBank and EMBL (the European Molecular Biology Laboratory nucleotide sequence database) were developed to accommodate this growth in sequence data, and were made available to the research community through the Internet. • Bioinformatics (or computational biology) is the name given to these computationally intense activities associated with the genome sciences. • Bioinformatics is also concerned with the analysis of proteins and other elements of cell biology, and their exploitation to develop therapeutic agents.

32. Gen Code and Pro Synthesis cont. • Genomics: Determination of the DNA sequence of genes and through the specialty of functional genomics, the identification of the functional role of these genes in cellular biology. • Proteomics: The study of all the proteins expressed within the cell. This includes determining the number, level, and turnover of all expressed proteins, their sequence, and protein interactions within the cell and across the cell membrane. • Transcriptomics: Study of mRNA molecules, which are involved in the transcription of DNA codes and their transport from the nucleus to the cell. • Glycomics: Study of cellular carbohydrates. • Metabolomics: Study of the small molecules generated in the synthetic and degradation pathways of cellular metabolism. • Pharmacogenomics: The identification of genetic markers that assist in predicting whether a patient will respond well to a therapy.

33. Gen Code and Pro Synthesis cont. • DNA and Cell: In almost all cells making up a living organism, there is an identical set of codes that regulate the function of the cell. This is encoded as one or more strands of the DNA molecule. The entire complement of DNA molecules of each organism is known as its genome. The overall function of the genome is to drive the generation of molecules, mostly proteins, which will regulate the metabolism of a cell and its response to the environment The genome is the same in almost every cell in the human body. For instance, a liver cell and a brain cell have the same DNA content and code in their nucleus. What distinguishes cells in one organ or tissue from one another is that different portions of their DNA are active. • DNA Structure: Each molecule of DNA may be viewed as a pair of chains of the nucleotide base molecules adenine(A), thymine (T), cytosine (C), and guanine (G). The two DNA strands join at each base-pairing, where A binds to T and C binds to G. DNA is able to undergo duplication, which occurs through the coordinated action of many molecules, including DNA polymerases (synthesizing new DNA), DNA gyrases (unwinding the molecule), and DNA ligases (concatenating segments together).

34. Gen Code and Pro Synthesis cont. • Transcription: In order for the genome to direct or effect changes in the cytoplasm of the cell, a transcriptional program needs to be activated to generate new proteins in the cell. DNA remains in the nucleus of the cell, but most proteins are needed in the cytoplasm of the cell where many of the cell's functions are performed. Thus, DNA must be copied into a transportable molecule called ribonucleic acid (RNA). A gene is a single segment of the coding region that is transcribed into RNA. RNA is generated from the DNA template in the nucleus of the cell through a process called transcription. • RNA: The RNA sequence of base pairs generated in transcription corresponds to that in the DNA molecules using the complementary A-T, C-G, with the principal distinction being that the nucleotide uracil (U) is substituted for the thymine (T) nucleotide. Thus, the RNA alphabetic ACUG instead of the DNA alphabet ACTG. The specific RNA that codes for proteins is called messenger RNA(mRNA).

35. Gen Code and Pro Synthesis cont. Flow of genetic information, from DNA to RNA to protein. This simplified diagram shows how the production of specific proteins is governed by the DNA sequence through the production of RNA.

36. Gen Code and Pro Synthesis cont. Protein Synthesis Illustrations

37. Gen Code and Pro Synthesis cont. Protein Synthesis Illustrations

38. Gen Code and Pro Synthesis cont. • Intron/Exon and Splicing: Genes are not necessarily continuous. Instead, most genes contain exons (portions of the gene that will be placed into the mRNA) and introns (portions that will not appear in the mRNA but are 'spliced out' during transcription). Introns are not inert, however, and some functions have been recently discovered for them, such as promoter-like control of the transcription process. Further, introns are not always spliced consistently. If an intron is left in the mRNA, an alternative splicing product is created. Various tissue types can flexibly alter their gene products through alternative splicing. • Protein Synthesis: After the splicing process, the mRNA molecule that has been generated is actively exported through nuclear pore complexes into the cell's cytoplasm. The cytoplasm is where the cellular machinery acts to generate the protein on the basis of the mRNA code. Specifically the ribosomal complex, which is a complex containing hundreds of proteins and special transfer RNA (tRNA) molecules, are directly involved in protein manufacture. A protein is built as a polymer or chain of amino acids, and the sequence of amino acids in a protein is determined by the mRNA template.(DNA) GCT TGC AGA GCG  (mRNA) GCUUGC AGA GCG  (protein chain) alanine cysteini argenine alanine*

39. Gen Code and Pro Synthesis cont. • Protein Processing: Once the protein is formed, it has to find the right place to perform its function, whether as a structural protein in the cytoskeleton, or as a cell membrane receptor, or as a hormone that is to be secreted by the cell. There is a complex cellular apparatus that determines this translocation process. One of the determinants of the location and handling of a polypeptide is a portion of the polypeptide called the signal peptide. This header of amino acids is recognized by the translocation machinery and directs the ribosome-mRNA complex to continue translation in a specific sub-cellular location, for example constructing and inserting a protein into the endoplasmic reticulum for further processing and secretion by the cell. • External/Internal Factors: Initiation of the transcription process can be caused by external events or by a programmed event within the cell. External factors such as piezoelectric forces, heat shock or stress, and the appearance of new micro- or macronutrients. Finally, there are pathological internal derangements of the cell that can lead to transcriptional activity. Self-repair or damage-detection programs may be internal to the cell, and can trigger self-destruction (called apoptosis) under certain conditions, such as irreparable DNA damage. There may be a deletion mutation of a repressor gene causing the gene normally repressed to instead be highly active.

40. Gen Code and Pro Synthesis cont. • Genome science is rich in sequence data but poor in functional knowledge. The volume of data must somehow be sifted and linked to human biology before it can have any meaning. • The central hypothesis (or hope) of these methods is that, with improved techniques, one can analyze larger data sets and discover the 'true' biological functional pathways in gene regulation, and identify the characteristics of disease that most accurately predict the nature and course of disease. Relative growth of Medline and GenBank. The cumulative growth of molecular biology and genetics literature (light grey) is compared here with DNA sequences (dark grey). Articles in the GS (molecular biology and genetics) subset of Medline are plotted alongside DNA sequence records in GenBank over the same time period

41. Gen Code and Pro Synthesis cont. • Treatment: Specifically, bioinformatics allows us to identify genes that indicate a patient's susceptibility to disease, assists in developing an understanding of the cellular pathways involved in generating the illness, and as a consequence provides an opportunity for the development of highly targeted therapies. Subcategories of B-cell lymphoma determined by microarrays correspond clinically to duration of survival. On the left is a dendrogram (similar to a decision tree) that has been constructed across the samples of B-cell lymphoma, using an unsupervised learning technique. The top branch essentially defines an even split between the categories GCB-like DLBCL and activated B-like DLBCL, but this distinction was never before made clinically. On the right are Kaplan-Meier survival curves of the patients from whom the samples were obtained. Patients whose cancer matched the Activated B-like DLBCL gene expression profile had a significantly worse prognosis

42. Gen Code and Pro Synthesis cont. • Microorganisms identification: The identification of microorganisms has historically relied on culturing organisms or morphological identification in specialized laboratories. However, the ability to identify microorganisms genetically is enabling the detection, identification and characterization of infective pathogens to be done near the patient, whether at the hospital bedside, in general practice or at home. • Pharmacogenomics: Bioinformatics analysis of genomic, pathological and clinical data from clinical trials can identify which sub-populations react well or poorly to a given drug  personalized 'molecular' medicine. • Drug discovery: once the entire genome of an infective microorganism is available, it can be examined for potential molecular target sites for attack by specially designed drugs. • Gene Therapies: For patients with genetically based chronic illnesses like cystic fibrosis, gene therapies are being pursued that should eventually offer the possibility of directly interacting with the defective genes to moderate, repress or disable the biochemical processes that result in the disease state.

43. Cell Division • Mitosis: In mitosis, one cell with the diploid number of chromosomes (the usual number, 46 for people) divides into two identical cells, each with the diploid number of chromosomes. This production of identical cells is necessary for the growth of the organism and for repair of tissues. • Meiosis: Meiosis is a more complex process of cell division that results in the formation of gametes, which are egg and sperm cells. In meiosis, one cell with the diploid number of chromosomes divides twice to form four cells, each with the haploid number (half the usual number) of chromosomes.

44. Cell Division cont. Stages of Mitosis

45. Cell Division cont. Stages of mitosis in a cell with the diploid number of four

46. Tissues and Membranes

47. Epithelial Tissue Simple Squamous Epithelium Stratified Squamous Epithelium Transitional Epithelium Simple Cuboidal Epithelium Simple Columnar Epithelium Ciliated Epithelium Glands Connective Tissue Blood Areolar Connective Tissue Adipose Tissue Fibrous Connective Tissue Elastic Connective Tissue Bone Cartilage Section Topics • Muscle Tissue • Skeletal Muscle • Smooth Muscle • Cardiac Muscle • Nerve Tissue • Membranes • Epithelial Membranes • Connective Tissue Membranes

48. Epithelial Tissue • A tissue is a group of cells with similar structure and function. Membranes are sheets of tissues. • Epithelial tissues are found on surfaces as either coverings (outer surfaces) or linings (inner surfaces). Because they have no capillaries of their own, epithelial tissues receive oxygen and nutrients from the blood supply of the connective tissue beneath them. Many epithelial tissues are capable of secretion and may be called glandular epithelium, or more simply, glands. • Classification of the epithelial tissues is based on: the type of cell, its characteristic shape, and the number of layers of cells. • There are three distinctive shapes: squamous cells are flat, cuboidal cells are cube shaped, and columnar cells are tall and narrow. • “Simple” is the term for a single layer of cells, and “stratified” means that many layers of cells are present. • Simple squamous epithelium is a: single layer of flat cells

49. Epithelial Tissue cont. Classification of epithelial tissues based on the shape of the cells and the number of layers of cells.

50. Epithelial Tissue cont. Types of Epithelial Tissue