BIOL 2200 Unit 1

Pathophysiology

Study of abnormal functions in normal bodily functions due to disease altering cells and tissues.

ways cells can be damaged

adaptation, injury, death, aging, and neoplasia

Pathology

The study of cells' physical changes from disease.

Signs

Objective, observable, or measurable things a sick person experiences (e.g. rash, blood pressure, swelling).

Symptoms

Subjective experiences that cannot be observed or measured by another person (e.g. weakness, nausea).

Diagnosis

The identification of the disease, disorder, or syndrome based on history or symptoms.

Syndrome

A cluster of signs and symptoms that change over time and characterize a particular condition.

Local

A small affected area where the injury or infection affects.

Systemic

An illness that affects the whole body or multiple organ systems.

Acute

A condition that lasts a short time.

Chronic

A condition that lasts a lifetime.

Remission

A reduction of symptoms of a disease that can be temporary or permanent.

Exacerbation

Times where disease progresses and a person feels significantly worse for a moment.

Etiology

The study of the origin of disease.

Pathogenesis

The development and progression of disease over time.

Prognosis

The predicted outcome of an illness or injury.

Communicable disease

Diseases that are transmitted from other people, animals, or the environment.

Degenerative disease

A chronic progressive condition resulting from cells, tissues, or organs deteriorating over time.

Idiopathic

A disease in which the cause is unknown.

Iatrogenic

A disease unintentionally caused by a health care practitioner or treatment.

Congenital

A disease present at birth.

Genetic disease

Diseases caused by a DNA mutation.

Risk factor

Factors that make the development of a disease more likely, but are not a direct cause.

Atrophy

decrease in cell size; found in the thymus gland and muscles

Hypertrophy

increase in cell size, often in skeletal muscle and heart muscle

Hyperplasia

increased number of cells due to cell proliferation; found in the liver and wound healing

Metaplasia

reversible replacement of a mature cell type with another cell type; found in smokers along respiratory tract

Dysplasia

Reversible abnormal change in cell size, shape, and organization; often found in cancer cells along cervix or respiratory tract

Intracellular accumulation

Buildup of materials (endogenous or exogenous) that a cell cannot metabolize.

Examples of endogenous Intracellular accumulation

excessive triglyceride deposits, lipofuscin

lipofuscin

a yellow-brown pigment that is seen in the liver and heart where neurons from accumulation of undigested material produced during normal cell structure turnover

excess triglyceride deposits

often common in alcoholics; liver cannot process all the fatty acids so it’s stored

Calcification

buildup of calcium salts in tissues due to calcium levels; happens in both normal and damaged tissues

Cell Injury

when the cell can no longer adapt to stress and cannot maintain homeostasis; caused by anything that disrupts the structure or deprives cells of oxygen

Hypoxia

Low oxygen in tissues due to ischemia or hypoxemia, leading to insufficient ATP production.

Hypoxemia

low oxygen in the blood often from decreased oxygen in air, loss of hemoglobin, or toxins and poisons

Three pathophyiological effects of hypoxia

reduced activity of ATP dependent sodium potassium pumps, decreased ATP production, and reduced activity of ATP dependent calcium pumps

effects of decreased ATP production

when oxygen is not available, it increases anaerobic respiration and lactic acid build up, which can lead to reduced activity of ATP-dependent enzymes and lead to necrosis, particularly made from lysosomes, mitochondria, and plasma membranes

reduced activity of ATP dependent sodium-potassium pump

when ion concentrations are altered, water enters the cell and causes cellular edema, so organelles get damaged, ribosomes are lost, and no protein synthesis

Free radical formation

Molecules with unpaired electrons in unstable atoms that want to steal electrons from healthy molecules.

Sources of free radicals

exogenous sources (x-rays, UV light, cigarette smoke) or endogenous sources (general metabolism, drug breakdown, or phagocytes)

Sources of protection against free radicals

enzymes and antioxidants

Failure of calcium homeostasis

Intracellular calcium pumps fail, causing calcium to build up in the cytosol and deploy degradative enzymes that damage cell membranes, nucleus, and ATP

Ischemia

Low blood flow in tissues resulting in reduced oxygen and nutrient delivery due to narrowed blood vessels.

Thrombus

A blood clot that forms within a blood vessel.

Embolus

A blood clot, fat, or air bubble that forms locally but breaks off and lodges in a smaller vessel.

Atherosclerosis

A disease that has fatty fibrous deposits in arterial walls.

Necrosis

Pathological cell death characterized by cellular swelling, rupture of cell membrane, and inflammation.

Apoptosis

Organized, regulated, and genetically programmed cell death carried out by caspases without inflammation.

Coagulative necrosis

Necrosis with cellular architecture held by protein denaturation; pale and firm, caused by ischemia, and found in heart, kidney, and spleen.

Liquefactive necrosis

necrosis that starts with a fungal or bacterial infection that results in dead tissue, which is broken by lysosomal hydrolytic enzymes into a liquid, pus-like mass; found in brain and abscesses

Caseous necrosis

Cheese-like necrosis with granulomas caused by usually tuberculosis; considered to be a combination of coagulative and liquefactive necrosis, found in lungs and lymph nodes.

Gangrene

Extensive tissue necrosis from severe ischemia and infection, appearing dark/black and dry or wet; found in toes, feet, and bowel

Fat necrosis

Firm, chalky opaque, white-yellow deposits in abdominal adipose tissue caused by pancreatitis or trauma; can combine with calcium to make soap in a process called "saponification"

Senescence theories of aging

Suggests aging is programmed in genes; evidenced by the Hayflick limit and telomere shortening.

Molecular theory of aging

Aging as a result of progressive accumulation of damage to biomolecules like DNA, proteins, and membranes.

Inflammation

a response by the immune system that is stimulated by any type of irritant or tissue damage (such a cut, trauma, burns, sprains, infections, ischemia, excessive heat or cold, lodged foreign objects), is characterized by 5 sgns, such as swelling/edema, heat, redness/erythema, pain and loss of function, and there two types of inflammation called acute and chronic

acute inflammation

inflammation that lasts for a few days, but can go for up to 6 weeks; it can be a localized response but can lead to more systematic symptoms, and the process is divided into two stages called vascular phase and cellular phase

chronic inflammaton

inflammation that lasts for months or years

key inflammatory cells

white blood cells, platelets, endothelial cells, pattern recognition receptors

pattern recognition receptors (PRR)

recognizes when the cell is foreign or damaged based on PAMP

pathogen associated molecular patterns (PAMP)

non-self proteins common to many pathogens, and include bacterial flagellin or lipopolysaccharides on bacterial cell walls

danger associated molecular patterns (DAMPS)

molecules common to damaged body cells, and include ADP, K + and enzymes

mast cells

can degranulate and release pro-inflammatory molecules, such as histamine

basophils

found in bloodstream and migrate to damaged tissue; involved with the allergic response and short-lived granulocytes

neutrophils

most numerous WBC and primarily eats pathogens, such as bacteria; they can degranulate to release toxic chemicals or NETs; they tend to live for short periods of time

left shift

a blood test where excessive neutrophils are detected; it often indicates an acute bacterial infection or severe inflammation

monocytes

when activated, can transform into a macrophage; tend to be activated after 24-36 hours to help with cleanup

Eosinophil

performs phagocytosis of foreign material, particularly of helminths, can help with allergic reactions, and have toxic-filled granules that are released to kill pathogens

Platelets

small fragments of cells that are critical for hemostasis and stops blood flow following damage to a vessel; they also secrete growth factors for growth and repair of tissue

Endothelial cell

epithelial cells that line blood vessel walls, act as a barrier between blood and tissues, and can call for white blood cells to come through the blood vessel to damaged wall

Natural killer cells

a lymphocyte that can kill other cells, such as damaged cells, abnormal cells, cancerous cells, or bacterially infected cells and extracellular pathogenic cells

Chemical mediators

substances that regulate and coordinate inflammation, made from cells or derived from plasma proteins produced in the liver

Histamine

released by mast cells, basophils, and (sometimes) platelets that can increase vasodilation and vascular permeability, and it can also cause bronchoconstriction, mucus production, itchiness, and chemotaxis of white blood cells

Arachidonic acid mediators

releases from the phospholipid component of cell members; it can enter the cyclooxygenase pathway to form prostaglandins and leukotrienes, which cause vasodilation, vascular permeability, and activate pain receptors

Prostaglandins

can do mediate vasodilation and increase vascular permeability

Leukotrienes

can increase vascular permeability

Cytokines

Glycoproteins that regulate cell signalling and play a big role in inflammation, anti-inflammation responses, and innate and acquired immunity; examples include interferons, interleukins, and tumor necrosis factors

Chemokines

smaller, cytokine-like proteins that induce chemotaxis

Complement proteins

plasma proteins that help activate acute inflammation, and certain proteins become activated to active different complement proteins that help the actions of the immune system, involved wth killng pathogens or intensifying inflammation; can be activated through the classical pathway, alternative pathway, or mannose-binding lectin pathway

Kinins

peptides produced by factor XII (Hageman factors); it produces bradykinin, which enhances the permeability of blood vessel walls, induce bronchoconstriction and activate pain receptions

Acute phase proteins

helps with activating complement cascade and binding to bacteria for phagocytosis assistance

Vascular Stage

damaged cells release cytokines and chemokines, mast cells are activated and release histamine, fluid and blood proteins leak into interstititil fluid to cause edema with vasodilaton and increased permeabilty of capillaries, released prostaglandins and bradykinin stimulates pain receptiors

exudate

fluid from blood vessels that collects in the tissues; functions as transport for leukocytes, antibodies, plasma proteins, transport of nutrients, and dilution of toxins; marker for acute inflammation

serous exudate

low protein fluid, similar to fluid under a blister

fibrinous exudate

increased inflammation s present, and vessels are more permeable, releasing more proteins in the tissue; fluid is sticky and thick

purulent exudate

severe inflammation accompanied by infection with lots of neutrophils, proteins, and tissue debris; large pockets of pus

Leukocytes Tissue Process

Contact with inflammatory chemicals, margination, adhesion, transmigration, chemotaxis, phagocytosis

Margination

Leukocytes move towards blood vessels and accumulate at endothelium

Adhesion

Endothelial cells develop adhesion molecules, like selectins, on their cell surface that bind to leukocytes, which can cause them to stick to vessel wall

Transmigration

Leukocytes migrate out of the blood vessels

Chemotaxis

Chemicals released by injured cells attract leukocytes to site of injury

Phagocytosis

leukocytes migrate and ingest foreign material

Cellular stage

Leukocyte invasion of tissue and phagocytosis

causes of chronic inflammation

low grade infections, irritants that can’t be removed from the body, and autoimmune diseases

Acute phase response

Release of cytokines, which can cause fever, anorexia, malaise, fatigue, and increase production of acute phase proteins

characteristics of chronic inflammation

dense infiltration of lymphocytes, macrophages, and fibroblasts; no exudate; more tissue damage; and possible development of cancer

granulomatous chronic infection

occurs when non-easily removeable particles become surrounded by mass of macrophages and lymphocyte, which forces macrophages to alter their shape to appear like epithelial cells and join multinucleate to engulf big particles; eventually the mass of cells is surrounded by connective tissue

effects of inflammation

tissue damage from phagocytes that release ROS and lysosomal enzymes, reduced blood flow that results in edema, and cancer due to growth factors

healing

can take up to 2 years and begins during acute inflammation; two types of healing called regeneration and replacement