Cell Function and Growth (Patho) - EG

Selective permeability

ability of the cell wall to allow some substances through the membrane and block others

Substances w/ free passage

• enzymes

• glucose

• electrolytes

Diffusion

movement of solutes towards lower solute concentrations

Facilitated diffusion

movement of solutes toward higher concentrations using a carrier molecule

Osmosis

passive movement of water/solvent across membrane toward higher concentrations (osmotic pressure)

• lysis and crenation

Active transport

movement against concentration gradient

Endocytosis

bringing substance into cell

• phagocytosis

• pinocytosis

Exocytosis

release of materials from the cell

Epithelial tissue acts as a…

barrier

• tightly packed cells

Connective tissue job

connects and supports other tissues

• cells suspended in extracellular matrix

Muscle tissue job

contracts to enable body movement

• consists of cell fibers w/ contractile proteins

Nervous tissue job

senses, processes and responds to stimuli

• consists of neurons and neuroglia

What do cells adapt to?

• changes in the internal environment

• to increased work demands by changing in size (atrophy/hypertrophy), number (hyperplasia) and form (metaplasia)

Atrophy

decrease in cell size

Causes of atrophy

• disuse

• denervation

• loss of endocrine stimulation

• inadequate nutrition

• ischemia or decrease blood flow

Hypertrophy

increase in cell size

• increase in tissue mass

• exercise = physiologic hypertrophy

Hypertension

left ventricular hypertrophy (pathologic hypertrophy)

Hyperplasia

increase in the number of cells

• 2 types: physiological and compensatory

Physiological hyperplasia

breast and uterine enlargement

Compensatory hyperplasia

regeneration of the liver after partial removal of the liver

Non-physiologic hyperplasia

excessive estrogen production —> endometrial hyperplasia and abnormal bleeding

• increased risk of developing endometrial cancer

Metaplasia

replacement of adult cells

• reversible change —> 1 adult cell (epithelial or mesenchymal) is replaced by another cell type

Examples of metaplasia

• trachea and large airways for smokers

• cervix during puberty or chronic irritation

Dysplasia

deranged cell growth of a specific tissue

• varies in shape, size and organization

• can be reversible if stimulus is removed

• ex.) cancers of respiratory tract and uterine cervix

Causes of dysplasia

• chronic irritation, inflammation or infection

• precursor to cancer

Intracellular accumulations

buildup of substances that cells cannot immediately use or eliminate

• some disorders are reversible such as hyperbilirubinemia that causes jaundice

3 categories of intracellular accumulations

1. normal: fatty liver

2. genetic: Tay-Sachs disease

3. pigment: Icterus (jaundice)

Dystrophic calcification

• occurs in dead/dying tissue

• deposit of calcium salts in injured tissue

• gritty grains —> hard rock material

• location: atheromatous lesions of advanced atherosclerosis ; areas of injury in aorta and large blood vessels

Metastatic calcification

• occurs in normal tissues

• increased serum calcium levels (hypercalcemia)

• location: long, renal tubules, blood vessels

Causes of metastatic calcification

• hyperthyroidism

• cancer w/ metastatic bone lesions

• immobilization

• vitamin D intoxication

Causes of cell injury

• physical agents

• chemical injury

• radiation

• biological agents

• low O2 levels

• nutritional imbalances

Apoptosis

programmed “suicide” of cells

• eliminates cells that are worn out, have been produced in excess, have developed improperly or have genetic damage

Ischemia

inadequate blood flow

Infarction

cells are damaged to the extent they cannot survive

Necrosis

cells swell and burst

• liquefaction, caseous fat, coagulative (ex. gangrene)

Free radicals

injurious, unstable agents that can cause cell death

Mechanical forces

• body impact w/ another object

• injury split and tear tissue

• fracture bones

• injure blood vessels

• disrupt blood flow

Low-intensity heat

partial thickness burns ; severe heat stroke

• cause vascular injury ; accelerate cell metabolism ; inactivates temperature-sensitivity enzymes ; disrupts the cell membrane

High intensity heat

coagulation of blood vessels and tissue

Cold

increases blood viscosity and induces vasoconstriction

• decrease in blood flow —> hypoxic tissue injury

• capillary stasis and arteriolar and capillary thrombosis

• edema results from increased capillary permeability

Electrical injuries

• tissue injury, disruption of neural and cardiac impulses

• alternating current is more dangerous than direction current

What do electrical injuries result in?

fractures and dislocation

• tissue damage caused by heat production in tissues —> most severe tissue injury occurs at the skin sites

When it comes to electrical injuries, the greater the skin resistance…

the greater the amount of local skin burn

When it comes to electrical injuries, the less the skin resistance…

the greater the deep and systemic effects

Effects of ionizing radiation exposure

• various types of cancers: skin, leukemia, osteogenic sarcomas, lung cancer

Effects of ultraviolet radiation exposure

sunburn and increased risk of skin cancer

Effects of non ionizing radiation exposure

• skin burns and thermal injury to deeper tissues

• involve dermal and subcutaneous tissue injury

Exposure to ethyl alcohol

harms gastric mucosa, liver, developing fetus, and organs

Exposure to acetaminophen

massive liver necrosis

Lead toxicity

• CARDINAL SIGN —> anemia

• cognitive and intellectual deficits ; neurobehavioral issues in children

• targets: RBCs, GI tract, kidneys and nervous system

Mercury toxicity

• source: long-lived fish such as tuna and swordfish

• young children and pregnant and nursing women should avoid the consumption of fish known for high mercury content

What do the heart, brain and kidney require to function?

large amounts of oxygen

• brain cells undergo permanent damage after 4-6 mins w/o oxygen

What occurs in hypoxic conditions?

• stimulation of RBC formation

• produce ATP in the absence of oxygen in the air

• respiratory disease

• ischemia

• anemia

• edema

• inability of cells to use oxygen

Normal process of programmed cell death

endometrial cells during menstrual cycle and the regression of breast tissue after weaning from breastfeeding

Interference w/ apoptosis cell death

neurogenerative disorders

• alzheimers

• parkinsons

• ALS

Liquefactive necrosis

• cells die, but their catalytic enzymes aren’t destroyed

• softening of the center of an abscess w/ discharge of its contents

Coagulative necrosis

• acidosis develops —> denatures enzymatic and structural proteins of cell

• hypoxic injury ; seen in infarcted areas

• an artery could be occluded by an embolus, thrombus etc

Gangrene

applied when mass of tissue undergoes necrosis

Dry gangrene

• affected tissue becomes dry and shrinks

• skin wrinkles and color changes to dark brown/black

• spread is slow

What does dry gangrene result from?

interference w/ arterial blood supply to a part w/o interference w/ venous return

• is a form of coagulative necrosis

Wet gangrene

• affected area is cold, swollen and pulseless

• skin is moist, black and tense

• blebs on surface —> liquefaction occurs —> odor produced

• spread is rapid ; no line of demarcation between normal and diseased tissues

Neoplasm (tumor)

rapid, uncontrolled, loss of differentiation

• may originate in one organ or spread from another site

What is carcinogenesis impacted by?

heredity and carcinogen exposure

Carcinogenesis 3 steps

1. initiation

2. promotion

3. progression

Benign

slow, progressive, localized, defined, differentiated more like host tissue

Malignant

rapid, metastatic, undifferentiated and fatal

Treatment goals are…

curative, palliative and/or prophylactic

• range from surgery to radiation to chemical modalities

Prognosis

likelihood of surviving cancer

Remission

cancer is considered “under control”

Gene

segment of DNA that is a template for protein synthesis

DNA

long chain of nucleotides called chromosomes

• 1 pair of sex chromosomes

Autosomes

22 sets of paired chromosomes

Karyotype

person’s unique set of chromosomes

Phenotype

physical expression of karyotype

Patterns of genetic inheritance

• homo vs. heterozygous

• dominant vs. recessive

How are autosomal dominant disorders transmitted?

from affected parents to offspring regardless of sex

Marfan syndrome (incurable, palliative treatment)

• FBN1 mutation reduces elasticity and increases growth factor

• diagnosis: examination, skin biopsy, genetic tests

Neurofibromatosis (incurable, treatment is palliative excision of tumors)

• type 1: NF1 defect causes nervous tumors and bone defects

• type 2: NF2 defect causes auditory nerve tumors

Autosomal recessive disorders occur only in…

homozygous allele pairs

Phenylketonuria/PKU

• diagnosed prenatally/at 3-day old serum screening

• PAH gene mutation leads to error converting the amino acid phenylalanine to tyrosine

Treatment of autosomal recessive disorders

• diet changes

• medication

• gene/enzyme therapy

Tay-Sachs (infantile, juvenile or adult)

• diagnosed through exam/serum level

• hexosaminidase A needed to metabolize lipids and prevent demyelination and nerve death

• normal infancy deteriorates into seizures, rigidity, blindness and death by age 5

Multifactorial disorders result from…

an interaction of genes and environmental factors

• may be expressed at birth or later

Cleft lip and palate (unilateral or bilateral deformities)

• improper formation of soft tissues in mouth and lips

• leads to feeding/nutrition issues

• risk factors: maternal smoking, diabetes and seizure medication

• diagnosed w/ prenantal ultrasound

• treated w/ surgery and speech therapy

Trisomy 21 (Down syndrome)

manifestations: upward slanted eyes, varying degrees of disability, organ defects/complications, strong relation to alzheimers

Monosomy X (Turner syndrome)

manifestations: gonadal streaks, distinctive physiology, aortic correction

Polysomy X (Klinefelter syndrome)

manifestations: small genitals, distinctive physiology, increased vulnerability to osteoporosis, breast cancer

Causes for teratogenic agents

• direct exposure of the preganant female and the embryo or fetus to the agent

• exposure of the soon to be pregnant female to an agent that has a slow clearance rate

• result of mutagenic effects of an environmental agent that occurs before pregnancy (causes permanent damage to female or male rep. cells)

Radiation: chemicals and drugs

• angiotensin-converting enzyme inhibitors (ACEI)

• angiotensin II receptor blocker (ARB)

• alcohol

• warfarin

• tetracycline

Agents: infectious disease

• measles

• mumps

• herpes simplex virus

• syphilis

• toxoplasmosis

Agents: fetal alcohol syndrome

• microcephaly

• epicanthal folds

• smooth philtrum

• small chin

• flat nasal bridge

• small palpebral fissures

• short nose

• thin vermilion border

Methods used for fetal diagnosis

• ultrasonography

• maternal serum markers

• amniocentesis

• chorionic villus sampling

• percutaneous umbilical cord blood sampling