pathophysiology pathos, disease, physis, nature, logos, science•Physiology is the study of normal, healthy bodily function. When something disrupts normal physiological processes, it enters the field of pathophysiology.•Pathophysiology is the study of functional changes in the body which occur in response to disease or injury. •This field is required study for most people who work in the medical profession, including doctors, nurses, and medical technicians. Understanding the progress of disease is key to learning how to identify and treat it.

Pathophysiology Course Second Semester 2010/2011(NURS 2301,3 credit Hours) by Dr.Mousa MH Elzabout ASSIST.PROF.,NURSING

COLLAGE ,IUG

Objectives of the course:After completing the course, students will be able to:

*Understand pathophysiologic concepts; homeostasis ,cell injury and death.

*Understand changes in cell growth ,cancer and metastasis.

*Describe methods of infection control. *Understand fluid and electrolyte imbalance,

acidosis and alkalosis. *Identify common genetic disorders as cystic

fibrosis, cleft lip and palate, Down syndrome, hemophilia, sickle cell anemia ..etc .

•knows common cardiovascular diseases as coronary artery disease,, hypertension and heart failure.

*Knows common respiratory diseases as respiratory distress syndrome ,respiratory failure, pneumonia…etc.

*Describes diseases of the nervous system as convulsions, cerebral palsy, head trauma, chorea, multiple sclerosis…etc.

*Describes gastrointestinal diseases as appendicitis, liver disease, intestinal obstruction, irritable bowel syndrome, malabsorption, peptic ulcer, pancreatitis ..etc.

* Identifies musculoskeletal diseases as gout, herniated disc, Perthes disease, muscle dystrophy, osteoporosis and osteomyelitis.

* Understands diseases of the hematologic system as anemia, polycythemia, thalasemia, thrombocytopenia and DIC.

*Knows immune system diseases as AIDS, systemic lupus erythematosis .

*Describes alteration of endocrine system as Addison’s disease, Cushing’s disease, diabetes and thyroid disorders.

*Identify common urinary system disorders as renal failure, infections, nephrotic syndrome ,calculi , glomerulonephritis.

.

* Describes diseases of the integumentary system as burns, dermatitis,pressure ulcers and psoriasis.•Understand reproductive system diseases as amenorrhea, prostatic hyperplasia, dysmenorrheal , endometriosis and hydrocele.Reference Textbooks

1-pathophysiology,A2-in-1 Reference for Nurses (2005),Lippincott Williams&Wilkins 2-Handbook of pathology ,Elizabeth J. Corvin, 3rd Edition, Copyright 2008,Lippincott Williams & Wilkins

Chapter 1Cell Structure and FunctionThe cell is the building block of each living organism. Each cell is a self-contained system that undergoes the functions of energy production, respiration, reproduction, and excretion. Cells join together to form tissues, tissues join to form organs, and organs form body systems.

Although cells differ as to their function in the body, all cells( in addition to cell membrane), contain the same internal structures . The inside of each cell can be divided into two main compartments: the cytoplasm

and the nucleus.

The CytoplasmThe cytoplasm includes everything inside the cell but outside the nucleus.It contains:

*The mitochondria are the energy sources of the cell. *endoplasmic reticulum and ribosomes are necessary for protein synthesis. *The Golgi apparatus is responsible for packaging and secretion of proteins synthesized on the ribosomes

*Intracellular lysosomes are vesicles that contain potent digestive enzymes .

*The internal skeleton, called the cytoskeleton, supports the cell from the inside and allows for the movement of substances inside the cell. The cytoskeleton also supports the movement of projections on the outside of cells, such as the hair-like projections

called cilia.

The Nucleus• The nucleus of the cell is a large, membrane-

bound organelle that contains deoxyribonucleic acid (DNA), the genetic material of the cell. To protect itself from breakage, the DNA is folded up inside the nucleus. Proteins responsible for folding and protecting the DNA are called histones.

Cell Membrane• A cell membrane encircles each cell. The cell

membrane is a semipermeable barrier composed of a bilayer of phospholipids, with interspersed, freely moving, protein molecules.

• Diffusion through the lipid bilayer is limited to lipid-soluble substances. For non-lipid substances to enter the cell, they must take advantage of the interspersed integral proteins.

Movement Through the Membrane- Lipid-soluble substances, such as oxygen, carbon dioxide, alcohol, and urea, move across the lipid bilayer by simple diffusion.- Other substances that are not lipid soluble, such as most small ions, glucose, amino acids, and proteins, move between the extracellular fluid and the intracellular compartments through pores provided by the integral proteins or through carrier-mediated transport systems.

Simple Diffusion Through the Cell MembraneThis process does not require energy, a substance that is permeable across the cell membrane will diffuse into or out of the cell until its concentration is equal on both sides. Osmosis:The diffusion of water into the cell is called osmosis. Osmosis occurs continually between intracellular and extracellular compartments, as water moves down its concentration gradient (i.e., from high concentration to low).

The drive for water to move in one direction or the other is described as the osmotic pressure. The osmotic pressure of a solution depends on the number of particles or ions present in the water solution. The more ions that are present in the solution, the less the water concentration and the greater the osmotic pressure (i.e., the pressure for water to diffuse into the solution).

A cell also has osmotic pressure. A dehydrated cell has high osmotic pressure i.e., low water concentration and high particle concentration. Water would diffuse into this cell if possible. An overhydrated cell has low osmotic pressure i.e., high water concentration and low particle concentration. Water would diffuse out of this cell if possible.

Active transport Active transport is mediated transport that requires energy . With active transport, energy is used by the cell to maintain a substance at higher concentration on one side of the membrane than the other. Examples of substances moved by active transport include sodium, potassium, calcium, and the amino acids. Each of these substances is actively transported, with the assistance of a carrier, in one direction against a concentration gradient.

Active transport Active transport is mediated transport that requires energy . With active transport, energy is used by the cell to maintain a substance at higher concentration on one side of the membrane than the other. Examples of substances moved by active transport include sodium, potassium, calcium, and the amino acids. Each of these substances is actively transported, with the assistance of a carrier, in one direction against a concentration gradient.

Facilitated diffusion Facilitated diffusion is similar to simple diffusion in that no energy is used by the cell to transport a substance but differs from simple diffusion in that it is assisted (facilitated) by a carrier and so can cross the membrane. Glucose moves into most cells by facilitated diffusion.

EndocytosisWhen large substances cannot enter the cell by diffusion or mediated transport, endocytosis (engulfment) of the substance by the cell membrane occurs.- Pinocytosis is the engulfment of macromolecules, such as protein, by vesicles.- Phagocytosis is the engulfment of dead cells or bacteria. Both processes require energy. Only cells of the immune system (i.e., macrophages and neutrophils) perform phagocytosis.

Energy ProductionCells are required to produce energy for their own use. Cells do this by extracting the energy contained in the chemical bonds of food molecules by combining the food molecules with oxygen inside the mitochondria of the cell. The food molecules used are glucose from carbohydrate metabolism, amino acids from protein metabolism, and fatty acids and glycerol from fat metabolism

The Sodium-Potassium PumpAn important example of active transport is the pumping of sodium and potassium across cell membranes. This transport depends on an integral carrier protein known as the sodium-potassium pump. The sodium-potassium pump transports sodium ions out of and potassium ions into the cell. This transport causes greater sodium concentration in the extracellular fluid (142 mEq/L) compared to the intracellular fluid (14 mEq/L), and greater potassium concentration in the intracellular fluid (140 mEq/L) compared to the extracellular fluid (4 mEq/L

The Effects of Pumping Sodium and Potassium 1- allows nerve and muscle function and action potentials to occur . 2- controlling cell volumeThe presence of intracellular proteins and other organic substances that cannot cross the cell membrane increases intracellular osmotic pressure and creates a tendency for water to diffuse into the cell. This diffusion of water, if unlimited, would cause the cell to swell and eventually burst. However, with the active transport of sodium ions out of the cell, the osmotic pressure inside the cell is reduced and the diffusion of water into the cell is contained.

Cell DivisionOnce duplicated, the chromosome pairs pull apart and the original cell splits into two cells. Each new cell contains the entire genetic information in 23 pairs of chromosomes. The process whereby a cell divides to produce two identical daughter cells is called mitosis. Meiosis, another type of cell division, occurs in the reproductive cells, the egg and sperm. Meiosis involves two cell divisions resulting in a total of four daughter cells produced, each containing 23 single chromosomes

rather than 23 pairs .

Cellular Replication and Division*Some cells, such as liver, bone marrow, and gut cells, undergo replication and mitosis frequently.*Nerve and cardiac muscle cells, do not replicate or divide except during fetal development or in the

neonatal period .

Pathophysiologic Concepts*Cells are continually exposed to changing conditions and potentially damaging stimuli. *If these changes and stimuli are minor or brief, the cell adapts to them. Cellular adaptations include atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia. More prolonged or intense stimuli can cause cell injury or death.

AtrophyAtrophy is a decrease in the size of a cell or tissue. Atrophy can occur as a result of : - disuse, for instance, as seen in the muscles of an individual who is immobilized . - decreased hormonal or neural stimulation of a cell or tissue, which is seen in the breasts of women after menopause or in skeletal muscle after spinal cord injury - nutritional deficiency and is seen in malnourished or starving people. - insufficient blood supply to cells, which cuts off vital nutrient and oxygen supply.

HypertrophyHypertrophy is the increase in the size of a cell or tissue. Hypertrophy is an adaptive response that occurs when there is an increase in the workload of a cell. The cell's demand for oxygen and nutrients increases, causing growth of most intracellular structures.Hypertrophy is primarily seen in cells that cannot undergo mitosis. Examples of these cells that experience hypertrophy are cardiac and skeletal muscle cells. There

are three main types of hypertrophy :

1-Physiologic hypertrophy occurs as a result of a healthy increase in the workload of a cell (i.e., increased muscle bulk through exercise).2-Pathologic hypertrophy occurs in response to a disease state, for example, hypertrophy of the left ventricle in response to longstanding hypertension .3-Compensatory hypertrophy occurs when cells grow to take over the role of other cells that have died. For example, the loss of one kidney causes the cells of the remaining kidney to undergo hypertrophy.

HyperplasiaHyperplasia is the increase in cell number as a result of an increased workload, or by hormonal signals. It can only occur in cells that undergo mitosis, such as liver, kidney, and connective tissue cells. Hyperplasia may be: 1-Physiologic hyperplasia occurs in endometrial cells .2-Pathophysiologic hyperplasia can occur with excessive hormonal stimulation, which is seen in acromegaly .3-Compensatory hyperplasia occurs when cells reproduce to make up for a previous decrease as what occurs in liver cells after surgical removal of sections of liver tissue. The compensation is striking in its rapidity.

Metaplasia Is the change in a cell from one subtype to another. The most common example of metaplasia is the change in the cells of the respiratory passages from ciliated columnar epithelial cells to stratified squamous epithelial cells in response to years of cigarette smoking. Stratified epithelial cells are better able to survive smoke damage. Unfortunately, they do

not assume the vital protective role of ciliated cells .

DysplasiaDysplasia results in cells that differ in shape, size, and appearance from their predecessors. It occurs in cells exposed to chronic irritation and inflammation. Dysplasia is not cancerous but indicates the possibility that a cancerous condition may occur.The most common sites of dysplasia are the respiratory tract and the cervix.

Cervical dysplasia usually results from infection of the cells with the human papilloma virus (HPV). Dysplasia is usually rated on a scale to reflect its degree, from minor to severe.

Cell InjuryCell injury occurs when a cell can no longer adapt to stimuli. This can occur if the stimuli are too long in duration or too severe in nature. Hypoxia, microorganism infection, temperature extremes, physical trauma, and radiation, cause cell injury.Cell DeathThere are two main categories of cell death:1-necrotic cell death, characterized by cell swelling and rupture of internal organelles. Common causes of necrotic cell death include prolonged hypoxia and

infection.

2 -apoptosis the dying cell shrinks on itself and then is engulfed by neighboring cells. Programmed cell death begins during embryogenesis and continues throughout the lifetime of an organism. Viral infection of a cell will often turn on apoptosis, ultimately leading to the death of the virus and the host cell. Deficiencies in apoptosis have been implicated in the development of

cancer .

Gangrene refers to the death of a large mass of cells. Gangrene may be classified as :1-Dry gangrene

-Spreads slowly with few symptoms -frequently seen in the extremities.

- often results from prolonged hypoxia.2-Wet gangrene -is a rapidly spreading.- often of internal organs.- is associated with bacterial invasion.- it exudes a strong odor and-is usually accompanied by systemic manifestations

3-Gas gangrene -infection of the tissue by a type of anaerobic bacteria called clostridium. - rapidly spreads to neighboring tissue as the bacteria release deadly toxins that kill neighboring cells.- muscle cells are specially susceptible and release characteristic hydrogen sulfide gas when affected.- this type of gangrene may prove fatal.

Wound RepairIf mitosis is posibleble and the area of necrosis is not too large, new cells of the same type fill in the empty space (regeneration). Scar tissue will form in if cell division is impossible or if the area of necrosis is extensive.Tissues that heal cleanly and quickly are said to heal by primary intention. Large wounds that heal slowly and with a great deal of scar tissue are said to heal by secondary intention.Tissue repair can be delayed if the host has: malnutrition, systemic disease, poorly functioning immune system or if there is reduced blood flow to the injured tissue or if an infection develops.

Conditions of Disease or Injury 1-HypoxiaHypoxia is the decreased concentration of oxygen in the

tissuesCauses : - inadequate intake of oxygen by the respiratory system. - inadequate delivery of oxygen by the cardiovascular

system. - lack of hemoglobin.• Oxygen is required by the mitochondria for oxidative

phosphorylation and the production of ATP. Without oxygen, this process cannot occur.

Consequences of Hypoxia :- When cells are deprived of ATP, they can no longer

maintain cellular functions, including the sodium-potassium pump. Without this , sodium diffuses into the cell drawing water and the cell begins to swell and burst

- Another consequence of hypoxia is the production of lactic acid, (which occurs during anaerobic glycolysis). Decreased ph causes damage to the nuclear structures.

• The effects of hypoxia are reversible if oxygen is returned within a certain period of time, the amount of which varies and depends on the tissue.

Clinical Manifestations of hypoxia• If the source of hypoxia is respiratory failure or myocardial

infarct, all tissues will be affected. Cell death may occur.• Increased heart rate.• Increased respiratory rate.• Muscle weakness.• Decreased level of consciousness

Complications of hypoxia• - Altered consciousness progressing to coma and death. • -Organ failure, including respiratory, cardiac or kidney failure.Treatment• Increase oxygen in inspired air through a mask or mechanical

ventilation.

2-Temperature Extremes• - Exposure to very high temperatures can cause burn

injuries, which directly kill cells or indirectly by causing coagulation of blood vessels or the breakdown of cell membranes .

• - Exposure to very cold temperatures injures cells in two ways:

• 1- constriction of the blood vessels that deliver nutrients and oxygen to the extremities

• 2-formation of ice crystals in the cells. These crystals can lead to cell lysis (bursting).

Prolonged exposure to cold can lead to hypothermia.

Clinical Manifestations of Cold Exposure and Hypothermia

- Numbness or tingling of the skin or extremities.

- Pale or blue skin that is cool to the touch.

- Shivering early on, then lack of shivering as condition worsens .

- Decreased level of consciousness , drowsiness, and confusion.

Complications - Blood clotting, characterized by pain and a decrease in

pulse downstream from the clot. If blood flow is inadequate, gangrene may result. - Frostbite .

-Ventricular dysrhythmia.

3-R ad iati o n In ju ry

-High-energy radiation (including ultraviolet radiation) is called ionizing radiation because it can displace electrons off atoms or molecules. Ionizing radiation is emitted by the sun, in x-rays,

and in nuclear weapons. -Low-energy radiation is called non-ionizing

radiation Effects of Ionizing Radiation -

May injure or kill cells directly by destroying the cell membrane and cell lysis. - May also lead to mistakes in DNA replication which may cause

programmed cell death or subsequent cancer.

• cells Susceptible to Ionizing Radiation Cells most susceptible to damage by ionizing radiation are cells that undergo frequent divisions, including cells of the gastrointestinal (GI) tract, the integument (skin and hair), and the blood-forming cells of the bone marrow.

Effects of Non-Ionizing Radiation

Non-ionizing radiation includes microwave and ultrasound radiation. The energy of this radiation is too low to break DNA bonds or damage the cell membrane.

Clinical Manifestations of Ionizing Radiation -Skin redness or breakdown .

- With high doses, vomiting and nausea caused by GI damage .

- Anemia if the bone marrow is destroyed . - Cancer may develop years after the exposure .

Treatment - Damage caused by low doses will be repaired and does not require treatment. - Cancers should be treated .

Pediatric Consideration

- Fetal cells rapidly undergo cellular division and are highly susceptible to the damaging effects of ionizing radiation.

- Infants and young children also experience periods of rapid cellular growth and are at risk of genetic damage from ionizing radiation.

Studies suggest that there are no apparent health risks to fetuses exposed to non-ionizing radiation .

4-Injury Caused by microorganismsMicroorganisms infectious to humans include bacteria, viruses, mycoplasmas, rickettsiae,

chlamydiae, fungi, and protozoa. Cells of the body may be destroyed

-directly by the microorganism or by a toxin released from the microorganism ,

-or indirectly injured as a result of the immune and inflammatory reactions.

• Clinical ManifestationsInfection by bacteria and viruses, often results in:- Regional lymph node enlargement- Fever (usually low-grade with a viral infection)- Body aches- Skin rash or eruption, especially with viral infections- Site-specific responses, such as pharyngitis, cough, otitis

media---etc.• Treatment- Bacteria and mycoplasmas are treated with antibiotics,

preferably after culturing the infection .- Certain viral infections may be treated with antiviral

agents. Other viral infections usually are left to resolve on their own.