Pathophysiology: Altered Cells & Tissues

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Pathophysiology: A Clinical Approach (2nd Ed.); Braun. Chapter 2.

Organs

fully differentiated body parts with specialized functions

Tissues

groups of different cell types that combine to form a specific function

Cells

basic units that make up tissues; sites where changes in structure and function lead to symptoms and diseases

Plasma Membrane

structure that protects the cell by creating barrier that separates intracellular components from extracellular environment surrounding it; comprised of lipids, carbohydrates, & proteins arranged in a bilayer

Bilayer

two interconnected layers

Lipid Bilayer composition

phospholipids (Phosphate  PO4-); phosphate connected to the lipid is the head

Tail

lipid structure of the lipid bilayer (phospholipid); composed largely of cholesterol; non-polar/hydrophobic

Bilayer arrangement

lipid layers align so non-polar tail portions are intertwined and polar heads line both outer and inner surface of the cell

Glycolipid

carbohydrate bound to lipid; makes up bilayer but in smaller numbers than phospholipids

Purpose of the bilayer

prevents unintentional passage of water-based substances by hydrophobic cell surface

Transmembrane Proteins

proteins that pass through the membrane which allow communication and transport between extracellular and intracellular environments

Integral Proteins

specific type of transmembrane protein that has tight binding to lipid tail and becomes part of membrane itself

Channel Protein

allows transport of ions (atoms with electrical charge) across plasma membrane

Cytoplasm

colloidal substance surrounding cell nucleus; composed of water, proteins, fats, electrolytes, glycogen, and pigments

Organelles

structures within a cell that perform a distinct function

Endoplasmic Reticulum

complex network of tubules, producing proteins & fats; important in regulation of ions within cell; subway-tubular transport system

Rough ER: contains ribosomes; synthesize proteins, produces lysosomal enzymes

Smooth ER: no ribosomes; synthesizes lipid, lipoproteins and steroid hormones regulation of Ca, detoxifies certain drugs & hormones

Golgi Apparatus

membrane structure; substances from ER go to GA and are packaged to be transferred out;
prepares substances produced by endoplasmic reticulum for secretion out of cell

ER=factory
GA=Packaging & shipping dept

Lysosomes

small sacs surround by membrane; digest cellular debris with hydrolytic enzymes; important in metabolism of particular substances

Perioxisomes

membrane-enclosed sacs smaller than lysosomes; contain enzymes (oxidase) that neutralize oxygen free radicals; promote cell survival by neutralizing harmful substances potentially damaging to cell

Protesomes

large, recognize abnormally folded or formed proteins; involved in proteolysis (breakdown of proteins)

Mitochondria

produces cellular energy source (ATP); contains cytochrome enzymes of terminal electron transport necessary for production of ATP; contains enzymes needed for the citric acid cycle, fatty acid oxidation, and oxidative phosphorylation

Genes vs. Chromosomes

Genes: Individual units of inheritance located on chromosome.

Chromosome: coiled structure of chromatin forms genetic code.

Cytoskeleton

Structure composed of tubule and filament structures that contribute to cell shape, movement, and intracellular transport.

Contains:
- Microtubules
- Microfilaments

Functions common to all cell types

Transportation
Ingestion
Secretion
Respiration
Communication
Reproduction

Semi-permeable Membrane

permits transport of some substance but acts as a barrier to others

Passive Transport

Substances enter cell passively with little energy required.

Diffusion (movement from higher to lower concentration) is an example of Passive Transport.

Concentration Gradient

movement from higher concentration to lower

Membrane Pore

membrane passage between extracellular and intracellular environments

Facilitated Diffusion

movement of some substances across membrane that need help of transport proteins for passage

Leak Channel

channel that opens without the need for stimulation

Gated Channel

channel that opens in response to stimulation

Ligand-gated Channel

stimulated by receptor-ligand binding

Mechanically-gated Channel

stimulated by vibration, stretching, and pressure

Active Transport

requires energy when transporting particles across membrane such as sodium potassium pump

Primary Active Transport

process requiring direct use of energy (ATP)

Secondary Active Transport

movement of a second substance depends on energy derived from active transport of primary substance

Contransport or Symport

systems in which substances are transported in same direction

Countertransport or Antiport

movement of substances in opposite directions

Endocytosis

process used to transport large substances into cells;

Two types:
Pinocytosis - ATP requiring process of ingesting small vesicles;
Phagocytosis - process of ingesting large particles such as cells, bacteria, damaged cell components

Exocytosis

vesicles move from Golgi into cytoplasm and then out of cell via cell membrane

Cellular Respiration

series of metabolic processes that transforms fuel molecules into energy (ATP) and waste products

Anaerobic Respiration

process of ATP production that occurs without oxygen

Aerobic Respiration

chemical reactions of oxidation and reduction between oxygen and nutrient products such as glucose

Glycolysis

process of breaking down glucose in cytosol of cells; occurs in absence of oxygen, releasing only small amount of energy

Feedback Mechanism

regulates gene activation to tightly control production of proteins and prevent cell damage caused by overproduction or underproduction

Ligand

signaling molecule; when ligand binds to receptor, it begins process of communication known as signal transduction pathway

Binding Affinity

tightness or strength of binding

Paracrine Signaling / Local Mediators

ligand receptor binding that results in signal transduction with a local effect

Endocrine Signaling

wider range of impact occurs when signal transduction affects cell behavior within entire organism

Hormones

ligands involved in endocrine signaling; process is slower and longer lasting than paracrine signaling

Proliferation

increase in cell number

Differentiation

changes in physical and function properties of cells, directs cells to develop into specific cell types

Responses to Stressors on Cells

adaptation or death;

mechanisms promote cell adaptation result from signals that cause changes in gene function; changes can be in size, number or structure

Atrophy

decrease in size of a cell

Why does atrophy occur?

decrease in functional demand (limb in cast);
decrease in oxygen supply to cell (ischemia);
nutrition deprivation;
aging process;
involution (removal of hormonal signals that stimulate growth)

Hypertrophy

increase in cell size usually from trophic or growth signals

Hyperplasia

increase in number of cells caused by hormone signaling

- High altitudes increase blood cells

Metaplasia

changing of one cell type to another;

adaptation can occur: for example, people with GERD have the cells of the esophagus change from squamous epithelium to glandular cell type. Also bronchial tube cells change to adapt in smokers.

Dyplasia

Refers to the actual change in cell size, shape, uniformity, arrangement and structure. In response to a chronic persistent stressor and is likely to resolve when the stressor is removed.

Bronchopulmonary Dysplasia

condition where stressors prompt cell alteration leading to chronic, irreversible tissue changes.

Caused by infants who need mechanical ventilation with high concentrations of oxygen.

Bronchial and alveolar tissue become thickened and reduce air into lungs

Apoptosis

physiologic and pathologic cell response to cellular signals. (A programmed cell death prompted by a genetic signals an is designed to replace old cells with new.
AKA Cellular suicide.
Could be due to damaged genetic material/mutation
Old age of the cell

Syndactyly

fusion or incomplete separation of digit soft tissue. This is an alteration in process of apoptosis.

Necrosis

death of cells related to injury

Some Causes of Injury to Cells

Infection
Physical injury
Mechanical injury
Thermal injury
Endogenous (toxins from within the body)
Deficit injury (such as oxygen deprivation)

Common Causes of Cell Injury & Death

"T-I-P-S"
Toxins (chemical, pathogenic)
Infections
Physical injury (mechanical, chemical, thermal)
Serum deficit injury (nutrition, hydration, oxygenation)

Cerebral Atrophy

reduction in size of the cells in the cerebrum of the brain; progression leads to reduction in brain tissue

Cardiac Hypertrophy

AKA Hypertrophic Cardiomyopathy
Disease of cardiac muscle that results from excessive workload and functional demand
Most common cause of sudden unexpected cardiac death in young individuals (< 30 yrs of age)

Reactive Oxygen Species (ROS)

toxic oxygen molecules or radicals that are formed by the reaction between oxygen and water during mitochondrial repiration.. Cell damage results from too many ROS or not enough available enzymes.
ROS damages DNA
Contributes to many diseases such as heart disease, diabetes, cancer

ROS AKA Free Radical Injury

Cerebral Atrophy's Effect on Neurons

Frontal & Temporal lobes: cognitive impairment
Hippocampus and cerebral cortex: Alzheimer's disease
Basal Ganglia: Movement disorders

Recovery is severely limited due to the inability of neurons to replicate.

Cause of Secondary Cardiac Hypertrophy

increased blood pressure resulting in increased workload on the ventricle

Primary Cardiac Hypertrophy Without Known Cause

inherited non-sex linked genetic autosomal-dominant trait

Compliance

ability of the ventricle to contract without rigidity

Syncope

fainting

Resting Left Ventricular Outflow Obstruction

When systolic pressure gradient reaches 30 mm Hg. It is moderate when it reaches 50 mm Hg or severe when it reaches 75 mm Hg.

Rx for Secondary Cardiac Hypertrophy

as soon as it manifests and before cells undergo permanent damage.
Treatment is geared toward relaxation of the ventricle and relief of the outflow obstruction.
Antihypertensive meds are used to lower resistance in left ventricle when hypertension is the cause.

Acromegaly

Condition of hyperplasia caused by hormone stimulation of excessive growth.
Manifested by abnormal growth of the hands and feet in people how have stopped growing (epiphyseal ossification occurs)

Usual Cause of Over-secretion of GH in Adults

pituitary tumor called an adenoma.

Gigantism

Same condition as Acromegaly but it occurs in youngsters
prior to the closure of epiphyseal growth plate.

Acromegaly, manifestations of

Altered facial features
Prominence of jaw, brow
Enlargement of tongue and lips
Pain & numbness in hands
Deepening voice
Snoring
Skin changes
Altered reproductive functioning
Breast discharge
Impotence

Rx for Acromegaly

Drug therapy
Radiation therapy
Surgical removal of adenoma

Chronic effects can be halted if identified early before permanent cell injury occurs.

Cells of the Cervix

Squamous epithelium (outer side of cervix & vagina)
Columnar epithelium (lines the endocervical canal)

Squamocolumnar Junction

Location at which the two types of cells merge. This area is dynamic throughout a woman's repro life, migrating and changing location on the cervix in response to stimuli such as hormones and pH.

The area where the cells types merge is called the transformation zone.

Metaplasia

Adaptations that these cell types undergo, changing from one type to another type of cell in response to environmental stressors.

Metaplastic changes of the cervix are not pathologic, the squamous epithelial cell component of the transformation zone is vulnerable to stressors which may cause the cells injure or damage.

Causes of Injury to Epithelium

Chronic infection
Irritation
Trauma

Cervical Dysplasia

considered a precancerous condition

Cervical Dysplasia - S&S

none

Cervical Dysplasia - Risk Factors

Early-onset sexual activity
Multiple (more than 3 sexual partners)
Exposure to human papilloma virus (HPV)
Smoking

Rx for Dysplastic Ectocervix Cell

Cryopsurgery
Cone biopsy/conization (with scalpel)
Large-loop electrosurgical excision (LEEP)

Cellular Damage - most common environmental cause

cigarette smoking

Hormone Process that causes Growth (gland & hormone)

Hypothalamus - GHRH
Pituitary - GH
Liver - Insulin-like growth factor 1 (1GF-1)
Hypothalamus - Somatostatin AKA GHIH

Hormone Process that causes Growth (gland & function)

Hypothalamus --;
Pituitary - causes cell cycle control responses/proliferation of cells;
Liver - promotes growth of bone, cartilage, soft tissue and organs;
Hypothalamus - Suppresses GH

Hormone Process that causes Growth (gland & stimulates)

Hypothalamus - pituitary to release GH;
Pituitary - liver to produce insulin-like growth factor 1 (1GF-1);
Liver - hypothalamus to produce somatostatin AKA GHIH;
Hypothalamus --.

Colloid

substance microscopically dispersed evenly throughout another substance

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