Advanced Pathophysiology Exam I

Disseminated Gonococcal Infection

Hemorrhagic pustules on an erythema base, often on extremities

Key Features: fever, arthralgia, tenosynovitis

Potential for septic arthritis and endocarditis

Rocky Mountain Spotted Fever

Petechial rash starting on wrists and ankles that spreads centrally

Key features: high fever, HA, hx of tick bite

Risk of systemic involvement including vasculitis and organ failure

Stevens-Johnson Syndrome

Painful red or purplish rash that spreads and blisters — leads to skin sloughing

Key features: usually drug induced or infection related, involves mucous membranes, can progress to TEN

Toxic Epidermal Necrolysis (TEN)

Widespread erythema, necrosis, and bullies detachment of the epidermis and mucous membranes.

Key features: often drug induced, severe pain

Risk of sepsis and multi organ failure

Meningococcemia

Petechial or purpuric rash, often starting on the trunk and lower extremities

Key features: rapid onset, fever, HA, neck stiffness

Potential progression to septicemia and shock

Staphylococcal Scalded Skin Syndrome (SSSS)

Diffuse erythema followed by blistering and desquamation, primarily in infants and young children

Key features: fever, irritability

Risk of dehydration and secondary infections

Kawasaki Disease

Polymorphous rash, often on trunk

Key features: fever for more than 5 days, conjunctivitis, strawberry tongue, swollen hands and feet

Risk of coronary artery aneurysm

Endocarditis

Petechiae, Janeway lesions, Osler nodes, Roth spots

Key features: fever, heart murmur

Potential for embolic events leading to organ damage

Henoch-Schonlein Purpura

Palpable purpuric rash, non-blanchable, often on buttocks, legs, and feet; can be accompanied by edema

Key features: affects children, preceded by URI

Pain, arthralgia, and renal involvement (hematuria, proteinuria)

Epigenetic Processes

DNA methylation

Histone modifications

Noncoding RNAs

Imprinting

Metaplasia

reversible replacement of one cell type for another

Atrophy

Decrease in cell size

Hypertrophy

Increase in cell size

Dysplasia

Abnormal change in cell size, shape, and organization

Often precancerous

Prokaryote

No true nucleus, no organelles

Eukaryote

Has nucleus, organelles, more complex

4 Major Categories for Organelle Function

Genetic control

Manufacturing, distributing, breaking down molecules

Processing energy

Communication between cells

Necrosis

Accidental cell death

Apoptosis

programmed cell death

Decrease in ATP production leads to…

Failure of sodium-potassium and sodium-calcium pump channels — water freely enters cell = cellular swelling — calcium accumulation = cell death

Reperfusion Injury can cause

Oxidative stress

Increase in free radicals

Inflammation

What prevents formation of free radicals?

Antioxidants

Senescence

cells stop dividing

Edema

Fluid pushed out of capillaries into tissue

Caused by increase in capillary hydrostatic pressure, leads to increase in capillary permeability

Renin-angiotensin-aldosterone system

Regulates BP and fluid balance

Elevated BNP levels mean…

Fluid overload + cardiac strain

Isotonic

No fluid shift

0.9% NS, LR

Hypotonic

Fluid shifts into cells

0.45% NS

Hypertonic

Fluid shifts out of cells

D5LR

What are the steps of phagocytosis?

Recognition and adherence

Engulfment

Infusion to form phagolysosomes

Exocytosis

Processes of epigenetics

DNA methylation

DNA hydroxymethylation

Histone modifications

Noncoding RNAs

Two X -chromosomes and one Y

Klinefelter Syndrome

DNA methylation

Associated with transcriptional silencing

Epigenetic process

DNA Hydroxymethylation

Associated with neural tube defects and disease severity in multiple myeloma

Histone modifications

Can up or down regulate gene expression

Noncoding RNAs

can alter activity of oncogenes and tumor suppressor genes

Innate Immunity

First line of defense

Skin, mucous, stomach acid

Opsonization

Process that makes bacteria more susceptible to phagocytosis

Complement System involves…

Opsonization

Anaphylaxtoxic activity

Cell lysis

What are some bacteria that are resistant to phagocytosis?

TB, Listeria, Leprosy, Typhoid fever, Brucellosis

Eosinophils

Primary defense against parasites

Basophils

Release histamines

B cells

Produce antibodies

Signs of Inflammation

Redness, Warmth, Pain, Swelling, Loss of Function

Interferons

Are released by infected cell to help neighboring cells resist infection

4 Phases of Wound Healing

Coagulation

Inflammation

Proliferation - Angiogenesis

Repair w fibroblasts

T cells

Coordinate immune response

Call cells to come help

Cytotoxic T cells

Attack and destroy infected cells

Natural active immunity

Acquired through infection

Natural passive immunity

Acquired through placenta and breast milk

Artificial active immunity

Vaccination

Artificial passive immunity

Admin of IG antibodies

Type I Hypersensitivity

Immediate, rapid reaction

Type II Hypersensitivity - cytotoxic

Antibodies bind directly to cells

Type III Hypersensitivity

Involves immune complex

Type IV Hypersensitivity

Delayed reaction

Type I Diabetes involves an attack on…

Pancreatic beta cells

Multiple sclerosis involves an attack on…

Myelin

Signs of bacterial infection

Pus, odor, neutrophil breakdown

Antigenic variation

How viruses can elude immune system

How do stress and elevated cortisol levels affect the immune system and wound healing?

Cause chronic inflammation — Suppress the immune response — delayed wound healing

Eczema

Dysfunction of skin barrier and immune activation — itchiness and redness

Psoriasis

A chronic autoimmune T-cell disorder causing excessive keratinocyte proliferation and silver plaques

What key enzyme does HIV use?

Reverse transcriptase — turns viral RNA into DNA

Acute HIV

Highly contagious

Flu-like s/s

Latent HIV

Slow decline of immune system

Asymptomatic

Virus continues to replicate but bone marrow can keep up

Acquire Immunodeficiency Syndrome (AIDS)

Th cell <200

Severe immunosuppression — allows for opportunistic infections

Allostatic overload

Chronic overstimulation of regulatory systems, can lead to onset of disease

Benign tumor

Encapsulated, well-differentiated, well-organized

Do not invade beyond their capsule

Malignant tumor

Rapidly growing

Loss of differentiation and organization

Hallmark of malignant tumor (10)

Anaplasia — loss of cellular differentiation

Replicative immortality

Tumor promoting inflammation

Invasion and Metastasis

Genomic instability

Inducing angiogenesis

Resisting cell death

Reprogramming energy metabolism

Uncontrolled Cellular proliferation

Avoiding immune destruction

What enzyme enable replicative immortality?

Telomerase

Cancer Stem Cells

Can change appear and function of cells to drive cancer progression

Warburg effect

Cancer cells produce ATP through glycolysis even in the presence of oxygen

Cancer from epithelial tissue

Carcinoma

Cancer from ductal or glandular structure

Adenocarcinoma

Cancer from connective tissue, bone, muscle

Sarcoma

Cancer from lymphatic tissue

Lymphoma

Cancer from blood forming cells

Leukemia

Carcinomas in Situ

Preinvasive

Could remain stable, progress to malignancy, or regress and disappear

“Guardian of the genome”

Tp53, tumor suppressing gene

Decides whether injured DNA will be repaired or undergo apoptosis

How does HPV progress to cancer

Prolonged infection leads to viral DNA being integrated into genomic DNA

Cachexia

Loss of muscle with or without fat loss

Cancer staging system

Stage 1 — cancer confine to organ or origin

Stage 2 — locally invasive

Stage 3 — spread to regional structures

Stage 4 — spread to distant sites

TNM system

System for staging cancer

T — tumor size

N — nodular involvement

M — metastasis

How are tumor markers used

Used to follow clinical course but not for initial diagnosis

Epidermis is made of…

Keratinocytes, melanocytes, Langerhans cells

Dermis is made of…

Connective tissue, blood vessels, nerve endings, glands

Hypodermis is made up of..

Adipose tissue

Functions of integumentary system

Protective barrier, thermoregulation, sensory reception, synthesis for vitamin d

Impetigo

Affects epidermis

Characterized by honey colored crusts around mouth

Tinea (ringworm)

Circular, scaly, red lesion with central clearing

Primary concern with Melanoma?

Tendency for early invasion and metastasis