318 Cellular Adaptation, Injury, & Death

Atrophy

Cells revert to a SMALLER size and LOWER level of functioning

• decreased O2 consumption

• decreased blood flow

• decreased protein synthesis

• can lead to entire tissue or muscle atrophy

Causes of atrophy

“use it or lose it”

• disuse: decreased skeletal muscle use

• denervation: disuse in muscles of paralyzed limbs

• loss of endocrine stimulation (hormonal changes)

• inadequate nutrition

• ischemia, decreased blood flow reducing exchange of nutrients to cells and other metabolic factors.

Hypertrophy

increase in cell SIZE and tissue mass

• can be normal in heavy lifting or exercise

• can be abnormal in cells that cannot multiply (cardiac or mature skeletal muscle)

• compensatory due to an initiating signal, grows until it reaches a limit

Hyperplasia

increase in NUMBER of cells in an organ or tissue

• activated by a stimulus, stops once stimulus is removed

• only in cells capable of mitotic division

• can be hormonal, compensatory, or due to growth factors

Hyperplasia can occur at the same time as hypertrophy

• Example: pregnancy when the uterus enlarges in both cell size and number of cells

Metaplasia

one adult cell type is REPLACED by another cell type that is more equipt to survive the surrounding conditions

• usually in response to chronic irritation or inflammation

• can be reversible once the irritant is removed

Example: smokers’ tracheal epithelial cells (ciliated columnar) are replaced by stratified squamous

Dysplasia

*THINK: disorganized

deranged cell growth results in cells that vary in size, shape, and organization

• could be from chronic inflammation

• could be a precursor to cancer, but does not necessarily lead to cancer (just something to watch for)

What are intracellular accumulations?

the buildup of substances that cells cannot immediately use or eliminate from the body

• can be too many lipids, proteins, etc.

• can be caused by errors in metabolism (endogenous) or environmental agents (exogenous)

Physical agents

Mechanical: split or tears in tissues

• fractured bones

• injured blood vessels

Extremes of temperature

• Cold: increases blood viscosity, vasoconstriction, reduced blood flow can cause hypoxic tissues (lack of O2)

• Heat: vasodilation, clotting of blood vessels and tissue proteins

Electrical: burns or electrical shocks

Radiation

Ionizing: free radicals are released and destroy cells

• above ultraviolet (left side of chart)

• causes swelling, vessel dilation, erythema, reversible necrosis or fibrosis

• used in cancer treatment

Examples: ultraviolet radiation, gamma rays, x-rays, cosmic ray photons

UV radiation: sunburn, damage is dependent on intensity, exposure time, and protective skin pigments present

Non-ionzing: causes vibration and rotation of atoms/molecules

• energy is converted to thermal energy

Chemical Agents

Drugs: directly or indirectly causes tissue damage

Lead toxicity: causes cognitive, intellectual, and neurobehavioral effects in children

targets RBCs, GI tract, kidneys, CNS

lead is absorbed in GI tract or lungs, stored in bones later

• paint

Mercury toxicity: causes toxicity to CNS and kidneys

• fish

• dental fillings

Biological Agents

viruses & bacteria that interfere with cell functions by disrupting or damaging cell structures

• can replicate and continue to injure cells

Nutritional Imbalances

Nutritional excesses

• high saturated fats

• high sugar

• obesity

Nutritional deficiencies

• iron deficiency

• protein deficiency

• scurvy - lack of Vitamin C

What are some mechanisms (causes) of cell injury?

• free radical formation

• hypoxia

• disruption of Ca homeostasis inside cells

What’s a free radical?

A highly reactive chemical species with an unpaired electron in the outer orbit (valence shell) that causes the molecule to be unstable

What causes free radicals?

ionizing radiation and some natural processes like metabolism

in normal cases, the body has antioxidants to contain free radical damage, but in serious cases (like radiation) then damage occurs

What does an antioxidant do?

donates an electron to the free radical’s unpaired electron to mitigate the effects of free radicals and stabilize the molecule

if there is no antioxidant present, the free radical will steal electrons from neighboring stable atoms, causing that atom to become a free radical, developing a chain of injuries

How does a free radical cause injury?

What happens when free radicals aren’t contained?

• damage to cell membranes

• inactivate enzymes

• damage to nucleic acids that make up DNA

Endogenous causes: metabolic processes and cell activities

Exogenous causes: UV and ionizing radiation

Oxidative stress occurs when the production of free radicals exceeds the body’s to neutralize/eliminate them

** This happens overtime but is linked to cancer & CV disease

What is oxidative stress from free radicals?

a cellular imbalance that occurs when the production of free radicals exceeds the body’s to neutralize/eliminate them

this imbalance causes a destructive chain reaction

Hypoxic cell injury

cells are deprived from oxygen

• produces local tissue damage

• cells that can revert to anaerobic metabolism will do this to maintain vital cell functions

  • anaerobic metabolism accumulates lactic acid and leads to acidosis (low pH, high H+)

• can be reversible if oxygen is restored

Examples of reversible cell injuries

Cellular swelling

Fatty change (intracellular accumulation of fats)

Define apoptosis

programmed cell death

highly selective

eliminates old or injured cells to control tissue regeneration

linked to cancer (not enough apoptosis) and neurodegenerative disorders (too much apoptosis)

PROGRAMED CELL DEATH MAINTAINS THE PLASMA MEMBRANE TO PREVENT INFLAMMATORY PROCESS

Necrosis

cell death due to injury, infection, toxins, or lack of blood flow

interferes with tissue regeneration

Example: Gangrene

NECROSIS DESTROYS THE PLASMA MEMBRANE, TRIGGERING THE INFLAMMATORY PROCESS

Gangrene (dry)

body part becomes dry, wrinkly, may shrink, change in color (brown/black), and interferes with arterial blood supply

• reduced blood supply, usually external (ex: limbs)

LINE OF DEMARCATION IS PRESENT

Gangrene (wet)

body part becomes cold, swollen, pulseless, moist, stinky, blebs may form on skin surface, and skin color is black under tension

• bacterial invasion, usually internal

NO LINE OF DEMARCATION IS PRESENT

Line of demarcation (Gangrene)

a clear line between healthy tissue and dead (necrotic) tissue

ARDS

Acute Respiratory Distress Syndrome (adults)

Why does ARDS occur?

post lung injury that leads to inflammatory process

• near drowning

• burns

• sepsis

• inhaled gas/toxins

Phases of ARDS

1. Injury or Exudative phase

2. Reparative or Proliferative phase

3. Fibrous phase

*THINK: Injury, Inflammation, Fibrosis

What occurs in the 1st phase of ARDS?

Injury/Exudative Phase

• increased permeability on both sides of the membrane

• impaired gas exchange

Clinical condition: refractory hypoxemia
low oxygen levels regardless of high oxygen supplementation

What happens in the 2nd phase of ARDS?

Reparative/Proliferative Phase

• increased neutrophils

• ARDS worsens in the presence of neutrophils

What happens in the 3rd phase of ARDS?

Fibrous Phase

• fibrous tissue replaces normal tissue

• further impairment of gas exchange

• lung tissue becomes dense/stiff

NOT EVERYONE REACHES THIS STAGE, THEY MAY RECOVER BEFORE FIBROUS TISSUE TAKES OVER

Clinical Manifestations of ARDS

dyspnea (SOB), tachypnea, cough, restlessness, fine or course crackles during auscultation, ABGs can be normal or altered

Respiratory Alkalosis typically manifests later, sometimes turning to Acidosis due to CO2 retention

Infant or small child respiratory disorder symptoms

• grunting during expiration

• nasal flaring

• shallow, fast respirations

• inspiratory retractions (soft tissues pull in between the ribs due to increased negative pressure in thoracic cage)

Respiratory distress syndrome in premature baby

1. decreased surfactant and immature lung structures

2. decreased lung compliance

3. atelectasis (partial or complete lung collapse)

4. hypoxia

5. increased pulmonary capillary permeability that causes edema and hyaline membrane formation of debris and lung fluid in the lungs

Name the 2 types of lung cancer

Non small cell lung cancer

Small cell lung cancer

SCLC IS MOST LIFE THREATENING

• metastases are fast and often found later on

• common in the brain

• small, round/oval cells that grow in clusters

Squamous cell carcinomas

common in the central bronchi, often pretty local

Adenocarcinoma

common in bronchial or alveolar lung tissues

MOST COMMON FOR NON-SMOKERS

Large cell carcinomas

common in lung peripheries

large cells, HIGHLY UNDIFFERENTIATED

spread easily

Clinical manifestations of lung cancer (local symptoms)

• chronic cough

• SOB

• wheezing

• hemoptysis (blood in the sputum, when cancer invades blood vessels)

• pain

Clinical manifestations of lung cancer (systemic symptoms)

• hoarseness

• superior vena cava syndrome

  • pleural effusion (fluid build up)

How do diagnose lung cancer

• biopsy

• chest x-ray

• bronchoscopy

• cytologic sputum studies

NSCLC diagnosis

TNM scale

SMLC diagnosis

graded limited or extensive

(combined to one area or spread all over)

Common cold overview

• caused by a virus

• spread via touching, and mucosal membranes (eyes, mouth, nose)

• stuffy nose, nasal drainage, headache, malaise, sore throat

Rhinosinusitis overview

• caused by virus, bacteria, or fungi

• severe allergies, URI, or obstruction of sinuses

• acute or chronic

• facial pain, headache, purulent nasal discharge, decreased sense of smell, fever

Influenza overview

• caused by virus (lungs) or bacteria (weakened immunity)

• types A, B, and C

• spread by droplets

• fever, chills, muscle aches, nonproductive cough, ear infection (otitis media), bronchitis

Sinuses

Frontal, ethmoid, maxillary

Infection is based on pain within them

Pneumonia

Inflammation of the lungs, usually due to infection

Atypical pneumonia

viral and mycoplasma infection that involves alveolar septum and interstitium of the lung

Typical pneumonia

bacterial infection that multiplies in the alveoli, causing inflammation and exudation of fluids into the air-filled spaces of alveoli

Risk factors for pneumonia

• extended hospital stays

• antibiotic therapies

• decreased cough reflex

• smoking

• diabetes

• viral infections

Stages of pneumococcal pneumonia

1. edema (pneumococci grows in alveolar spaces)

2. red hepatization (inflammation - neutrophils and RBCs)

3. grey hepatization (macrophages engage in phagocytosis to clean up debris)

4. resolution (alveolar exudate is removed and scar tissue may form)

Whaat causes pneumococcal pneumonia?

Streptococcus pneumoniae, a gram + diplococcus bacteria that causes inflammation and fluid accumulation in the alveoli, leading to pneumonia.

Clinical manifestations of pneumococcal pneumonia

• acute

• malaise

• shaking

• fever

• productive cough

• limited breath sounds

• loss of appetite

• older adults: decrease in mental status

Which of the following have a PRODUCTIVE cough?

pneumococcal pneumonia

Legionnare Disease overview

caused by the bacteria Legionelle pneumophila, a gram negative rod

It’s spread via water sources (inhaled or aspirated)

the disease impairs gas exchange due to fluid in the lungs

Clinical manifestations of Legionnare Disease

malaise, weakness, lethargy, fever, dry cough, diarrhea, confusion, and hyponatremia (low Na)

Tuberculosis overview

caused by aerobic bacteria

spread by airborne droplets, and eating contaminated food or water

Clinical courses of TB

• failure to register infection (asymptomatic)

• become infection but clear/cure it

• harbor the infection but not contagious (latent)

• progressive/active TB that is contagious

Clinical manifestations of TB

fever, night sweats, weight loss, fatigue, SOB, fine lung crackles, and dry → productive cough overtime

When are latent TB tests positive/negative?

Skin and blood test for latent TB are always positive

Xray will remain negative unless TB transitions to active state

Describe the progression of TB

1. inhaled contaminated droplets

2. macrophages engage in phagocytosis (BUT CANNOT KILL TB BY THEMSELVES)

3. type 4 hypersensitivity initiated (cell mediated, T cells)

4. T cells activate and tell macrophages to release enzymes that kill TB

5. lung damage throughout this process

6. granulomas form with caseating (cheese looking) necrosis

Once antibiotics administered: granulomas heal, shrink, and typically leave scarring

Fungal infections overview

a type 4 hypersensitivity, leading to granulomas that resemble TB

caused by an inhalation of spores

fungi can usually be determined based on your location in the US

people with HIV, diabetes, and taking immunosuppressives are at higher risk for developing severe fungal diseases

What are some examples of viral illnesses?

RSV, influenza, COVID, HIV, HPV, chix pox, measles

What are some examples of bacterial illnesses?

Rhinosinusitis, Pneumonia, Legonnaire disease, Tuberculosis

What are some examples of fungal illnesses?

Candida, ringworm, athletes foot

What are some examples of helminths?

roundworms and tapeworms

Modes of transition (of pathogens)

penetration

direct contact

ingestion

inhalation

Describe penetration

disruption of the integrity of the skin or mucous membrane

SKIN IS NOT INTACT

Describe direct contact

Direct transmission from infection tissue/secretion to an exposed INTACT mucous membrane

Describe ingestion

transmitted via oral cavity and GI tract

Describe inhalation

inspired pathogen that bypasses defense mechanisms (hair, epithelia, etc.)

enters the respiratory system

Nosocomial

healthcare associated or developed in a facility

Common substances of transmission

blood, saliva, feces, urine, respiratory secretions, body fluids

Virulence factors

toxins

adhesion factors

evasive factors

invasive factors

Toxins

substances that alter or destroy normal host cell functions

Adhesion factors

the pathogen has the ability to attach and colonize the host

Evasive factors

the pathogen has the ability to hide or avoid the host’s immune system

example: avoid phagocytosis

Invasive factors

pathogen penetrates anatomic barriers and host tissues to invade cells

Name the phases of the disease course

Infection (transmission of pathogen)

Incubation (time between pathogen entering and symptoms arising)

Prodromal (non specific symptoms)

Acute (increasing symptoms, likely specific)

Convalescent (decreasing symptoms and tissue repair)

Resolution (elimination of pathogen)

Criteria for infectious disease

the host must sustain injury or pathologic damage

evidence of the pathogen must be present in infected site(s)

clinical signs and symptoms must be compatible with the infectious process

HPV - VIRAL

Genital WARTS, cervical dysplasia, ASYMPTOMATIC, CURABLE

CAULIFLOWER shaped lesions on internal and external genitalia

transmission: vaginal, oral, and anal sex

HSV - VIRAL

Genital HERPES, ASYMPTOMATIC, ALWAYS PRESENT IN THE BODY ONLY MANAGE FLARE UPS

SMALL LESIONS THAT RUPTURE, tingling, itching, pain, DYSURIA, URINE RETENTION, SYSTEMIC SYMPTOMS

transmission: vaginal, anal, oral sex and childbirth

VIRAL

Zika - VIRAL

BRAIN EFFECTS, MIND INFECTION, ASYMPTOMATIC

FEVER, RASH, JOINT/MUSCLE PAIN, CONJUNCTIVITIS (eye inflammation)

transmission: vaginal, oral, anal sex, mosquito bites, or perinatal (become infected while pregnant)

Bacterial Vaginosis - BACTERIAL

MICROFLORA OVERGROWTH

NEED 3 of 4: THIN, WHITE-GREY DISCHARGE, FISHY ODOR, pH >4.5, OR CLUE CELLS

transmission: vaginal sex

Chlamydia - BACTERIAL

ASYMPTOMATIC, CERVICAL DISCHARGE, HYPERTROPHY, REITER SYNDROME: urethritis, conjunctivitis, arthritis, lesions on palms and soles

transmission: vaginal, anal, and oral sex

Gonorrhea - BACTERIAL

ASYMPTOMATIC, DYSURIA (burning during urination), PAINFUL INTERCOURSE, BLEEDING, PROCTITIS (rectal inflammation),

CAN AFFECT PROSTATE, EPIDIDYMIS, PERIURETHRAL GLANDS, FALLOPIAN TUBES, OR CAN LEAD TO STERILITY

transmission: vaginal, anal, oral sex, and perinatal

Syphilis - BACTERIAL

3 STAGES:

1ST: PAINLESS CHANCRE

2ND: RASH, FEVER, SORE THROAT, INFLAMED EYES, CONDYLOMATA LATA

3RD: LESIONS (GUMMAS: in the CNS and CV system, cause blindness, memory issues, and heart problems)

transmission: vaginal, anal, oral sex, and perinatal

Candidiasis - FUNGAL

MICROFLORA OVERGROWTH

THICK WHITE DISCHARGE, ODORLESS, VULVOVAGINAL ITCHING/BURNING, PAINFUL INTERCOURSE, pH <4.5

transmission: vaginal sex

Trichomoniasis “Trich” - PROTOZOA

ASYMPTOMATIC, VAGINITIS, EXCESSIVE GREEN/YELLOW/FROTHY DISCHARGE, STRAWBERRY SPOTS ON CERVIX, pH >6

INCREASES RISK OF PELVIC INFLAMMATORY DISEASE, PREMATURE BIRTH, AND INFERTILITY

transmission: vaginal, anal, and oral sex

What is the main difference between BV and Candidiasis

The pH!

BV: >4.5 and fishy odor

Yeast: <4.5 and odorless

Define immunodeficiency

an abnormality in 1+ parts of the immune system that results in an increased susceptibility to disease states that would normally be eliminated by a properly functioning immune system

Primary vs. Secondary immunodeficiency

Primary: congenital (present at birth) or inherited (inherit a gene)

Secondary: acquired later in life

Name the 2 types of immunity

Innate → phagocytosis & complement

Adaptive → cell-mediated & humoral

Disorders of phagocytosis (INNATE)

Cells fail to do phagocytosis

Cells fail to do apoptosis or do too much apoptosis

Example: Chronic granulomatous disease

Disorders of the complement system

Failure to recruit inflammatory cells

Failure to do opsonization (flagging) of pathogens

Failure to kill pathogens

Protein malfunctions to maintain immune control

Example: Angioneurotic edema

Humoral (B-cell) immunodeficiencies

Any B-cell dysfunction

Decreased Ig production

Example: Selective deficiencies of IgG, IgA, or IgM

B cell life cycle

B cells → plasma cells OR memory cells → immunoglobulins (proteins that form antibodies) → secrete antibodies

**Memory cells do not finish this pathway, they only remember antigens at the next exposure to ensure a quick immune response

Cell-mediated (T-cell) immunodeficiencies

Any T-cell dysfunction

• Helper T-cells (directors/taggers)

• Cytotoxic T-cells (killers)

Example: HIV or malignant tumors

Combined immunodeficiency syndrome

Occurs when B and T cells are both affected, causing issues in adaptive immunity functions

Examples: radiation, immune suppression, or cytotoxic drugs