Unit 1: Concepts of Health and Disease

Unit 1: Concepts of Health and Disease

• Pathogenesis: the sequence of cellular and tissue events that occur from the time of initial contact with an etiologic agent until the ultimate expression of a disease.
• Morphology: refers to the fundamental structure or form of cells or tissues, including gross anatomic and microscopic changes characteristic of a disease.
• Histology: the study of cells and extracellular matrix of body tissues, with histologic sections playing a crucial role in diagnosing many types of cancers.
• Clinical Manifestations: the signs and symptoms that indicate the presence of a disease, such as fever.
• Diagnosis: the designation of the nature or cause of a health problem, requiring a careful history, physical examination, and diagnostic tests.
• Clinical Course: the evolution of a disease, which can be acute, subacute, or chronic.
• Disease: an acute or chronic illness that one acquires or is born with, causing physiologic dysfunction in one or more body systems.

Unit 2: Cellular Adaptation and Cell Injury

• Hyperplasia: an increase in the number of cells in an organ or tissue, occurring in tissues with cells capable of mitotic division, such as the epidermis, intestinal epithelium, and glandular tissue.
  • Physiologic hyperplasia: e.g., breast and uterine enlargement during pregnancy.
  • Nonphysiologic hyperplasia: e.g., excessive estrogen production causing endometrial hyperplasia.
• Metaplasia: a reversible change in which one adult cell type is replaced by another, often in response to chronic irritation and inflammation.
  • Example: adaptive substitution of stratified squamous epithelial cells for ciliated columnar epithelial cells in the trachea and large airways of a habitual cigarette smoker.
• Dysplasia: deranged cell growth of a specific tissue, resulting in cells that vary in size, shape, and organization.
  • Example: dysplastic changes in cancers of the respiratory tract and uterine cervix.
  • Pap smear: a diagnostic tool used to detect cervical dysplasia and cancer.
• Necrosis: cell death in an organ or tissue, characterized by liquefaction, coagulation, or caseous necrosis.
  • Liquefaction Necrosis: occurs when some cells die, but their catalytic enzymes are not destroyed.
  • Coagulation Necrosis: characterized by acidosis, denatured enzymatic and structural proteins, and commonly seen in infarcted areas.
  • Caseous Necrosis: a form of coagulation necrosis in which dead cells persist indefinitely, commonly found in the center of TB granulomas.
• Ischemia: impaired oxygen delivery and impaired removal of metabolic end products, affecting local tissue injury.
• Infarction: occurs when an artery supplying an organ or part of the body becomes occluded, and no other source of blood supply exists.

Unit 2: Cellular Adaptation and Cell Injury (continued)

• Intracellular Accumulations: the buildup of substances that cells cannot immediately use or eliminate, such as beta-amyloid fragments.
• Pathologic Calcifications: the deposition of calcium salts in injured tissue, including dystrophic and metastatic calcifications.
  • Dystrophic Calcifications: occur in dead or dying tissues, and are often visible to the naked eye.
  • Metastatic Calcifications: occur in normal tissues as a result of increased serum calcium levels.
• Injury from Physical Agents: e.g., lead poisoning, which can cause toxic effects on the body, including anemia, GI tract disturbances, and neurological damage.

Unit 3: Genetic Control of Cell Function

• Genetic Control: the process by which genes regulate cellular function, from gene transcription to protein synthesis.
• Screening, Diagnosis, and Treatment: various methods used to detect and diagnose diseases, including tumor markers, Papanicalaou test, tissue biopsy, immunohistochemistry, and microarray technology.

Genetic and Congenital Disorders

• Period of Vulnerability: the time interval during which the embryo's development is most easily disturbed, extending from day 15 to day 60 after conception.
• TORCH Infections: a group of infectious agents that can cause congenital anomalies, including toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes.
• Folic Acid Deficiency: a risk factor for neural tube defects, such as anencephaly, spina bifida, and encephalocele.
• X-Linked Recessive Inheritance: a pattern of inheritance in which a defective gene is located on the X chromosome and is recessive, affecting males who inherit the mutant copy.
• Marfan's Syndrome: an autosomal dominant disorder of the connective tissue, affecting the eyes, cardiovascular system, and skeletal system.

Unit 4: Stress and Adaptation

• Stress Response: the body's response to stress, including the activation of the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis.
  • Acute Stress: a short-term response to stress, characterized by the fight-or-flight response.
  • Chronic Stress: a long-term response to stress, which can lead to pathophysiologic changes and health problems.
• Edema: palpable swelling produced by the expansion of the interstitial fluid volume, which can be assessed and treated in various ways.
• Acid-Base Regulation: the process by which the body maintains a stable pH, involving the lungs, kidneys, and chemical buffers.

Unit 4: Infectious Diseases

• Diagnosis and Treatment of Infectious Diseases: the detection and diagnosis of infectious diseases, including culture, serology, and antigen detection.
• Infectious Diseases: various diseases caused by infectious agents, such as bacteria, fungi, and viruses.### DNA and RNA Sequencing
• DNA probe hybridization: small fragments of DNA are cut from a specific pathogen's genome and labeled with compounds for detection
• Polymerase chain reaction (PCR): incorporates two unique reagents: a specific pair of oligonucleotides (primers) and heat-stable DNA polymerase

Infectious Diseases

• Diagnosis and treatment of infectious diseases
  • Antimicrobial agents:
    • Antibacterial agents (antibiotics): effective only against prokaryotic organisms, bactericidal or bacteriostatic
    • Antiviral agents: interrupt viral replication, protease inhibitors for HIV
    • Antifungal agents: target cytoplasmic membranes of yeasts or molds
    • Antiparasitic agents: exploit essential components of parasite metabolism or cellular anatomy
  • Immunotherapy: supplements or stimulates host immune response
  • Surgical intervention: removal of infected tissues, organs, or limbs

Innate and Adaptive Immunity

• Epithelial barriers: intact skin and epithelial cells lining gastrointestinal, respiratory, and urogenital tracts
• Innate immune response: recognition of common surface receptors on invading microorganisms by leukocytes
• Infectious disease terminology:
  • Toxin: produced by bacteria
  • Infection: presence and multiplication of another living organism within a host
  • Colonization: act of establishing a presence
  • Microflora: internal and external exposed surfaces of the human body normally inhabited by bacteria
  • Mutualism: interaction benefiting both microorganism and host
  • Parasitic relationship: only the microorganism benefits
  • Infectious disease: injury or pathologic damage caused by a microorganism

Passive Immunity and Immunoglobulins

• Passive immunity: immunity transferred from another source
• Adaptive immunity: acquired through host immune response to an antigen
• Immunoglobulins (Igs):
  • Classified into 5 categories based on role in humoral defense mechanism
  • Comprised of four polypeptide chains with at least two identical antigen-binding sites

Anaphylaxis

• Catastrophic, systemic, life-threatening IgE-mediated hypersensitivity reaction
• Clinical manifestations: graded on a scale of I to IV, with increasing severity
• Prevention and management: focus on withdrawal of offending allergen, maintenance of patent airway, and administration of epinephrine

Innate Immunity Barriers

• Protect humans against pulmonary infections
• Include physical barriers, such as the skin and mucous membranes

Metabolic Requirements of Nervous Tissue

• High rate of metabolism, requiring 15-20% of total resting cardiac output and consuming 20% of oxygen
• Interruption of blood or oxygen supply leads to clinically observable signs and symptoms

Somatosensory Function, Pain, Headache, and Temperature Regulation

• Types of pain:
  • Acute pain: elicited by injury to body tissues and activation of nociceptive stimuli
  • Chronic pain: persists longer than expected after an inciting event
  • Cutaneous pain: arises from superficial structures
  • Deep somatic pain: originates in deep body structures
  • Visceral pain: originates in visceral organs
  • Referred pain: perceived at a site different from its point of origin

Disorders of the Motor Unit and Neuromuscular Junction

• Myasthenia gravis:
  • Disorder of transmission at the neuromuscular junction
  • Antibody-mediated attack on the nicotinic AChR or muscle-specific tyrosine kinase
• Neuromuscular junction:
  • Synapse between a motor neuron and a skeletal muscle fiber
  • Transmission of impulses mediated by the release of acetylcholine from axon terminals

Disorders of Motor Function

• Multiple sclerosis:
  • Characterized by inflammation and destruction of mostly the white matter of the CNS
  • Lesions consist of hard, sharp-edged, demyelinated patches throughout the white matter
• Parkinson's disease:
  • Degenerative disorder of basal ganglia function
  • Resulting in variable combinations of tremor, rigidity, akinesia/bradykinesia, and postural changes

Mechanisms of Brain Injury

• Primary brain injuries: damage caused by impact, including focal (contusion, laceration, hemorrhage) or diffuse (concussion, diffuse axonal injury)
• Secondary brain injuries: damage resulting from subsequent brain swelling, infection, or cerebral hypoxia
• Hematomas:
  • Epidural: develops between the inner table of the skull and the dura
  • Subdural: develops between the dura and the arachnoid
  • Traumatic intracerebral: single or multiple, occurring in any lobe of the brain
• Stroke:
  • Ischemic: caused by cerebrovascular obstruction by thrombosis or emboli
  • Hemorrhagic: most frequently fatal, resulting from the spontaneous rupture of a cerebral blood vessel

Disorders of Brain Function/Cerebrovascular Disease/Stroke

• Clinical manifestations: determined by the cerebral artery affected, the area of brain tissue supplied, and the adequacy of collateral circulation
• Always sudden in onset and focal, usually one-sided
• Symptoms include facial droop, arm weakness, slurred speech, unilateral numbness, vision loss, language disturbance, and sudden unexplained imbalance or ataxia

Neurocognitive Disorders

• Alzheimer's disease:

  • Diagnosis based on clinical findings, neuroimaging, and metabolic screening
  • No curative treatment, but medications can slow progression and improve depression, agitation, or sleep disorders

• Guillain-Barré syndrome:

  • Acute immune-mediated polyneuropathy
  • Characterized by rapidly progressive ascending symmetrical limb weakness and loss of tendon reflexes
  • Treatment includes support of vital functions, prevention of complications, and plasmapheresis and high-dose intravenous immunoglobulin therapy

• Schizophrenia:

  • Neurophysiology of symptoms: changes in dopamine and serotonergic systems, decreased glutamate activity, and other neurotransmitter changes

• Mood disorders:

  • Neurophysiology of symptoms: interactions between biologic and psychosocial factors, inflammation, HPA axis hyperactivity, low levels of neurotrophic growth factor, and low levels of vitamin D### Strabismus (Squint)

• Abnormality of eye coordination or alignment that results in loss of binocular vision

• Can be divided into two forms: nonparalytic (concomitant) and paralytic (nonconcomitant)

• Nonparalytic form: no primary muscle impairment

• Paralytic form: weakness or paralysis of one or more of the extraocular muscles

• Can be intermitted or periodic, with periods of parallel eyes

Amblyopia (Lazy Eye)

• Decrease in visual acuity resulting from abnormal visual development in infancy or early childhood
• Vision loss ranges from mild (worse than 20/25) to severe (legal blindness, 20/200 or worse)

Conjunctivitis

• Allergic: characterized by itching, bilateral tearing, itching, and redness of the eye
• Treatment: allergen avoidance, cold compresses, eye washes with tear substitute, and oral antihistamines
• Viral: common cause is adenovirus, symptoms include generalized conjunctival hyperemia, copious tearing, and minimal exudate
• Bacterial: burning, tearing, mucopurulent or purulent discharge, usually begins in one eye and spreads to the other
• Treatment: antibiotic drops or ointments, except for N. gonorrhoeae which requires systemic antibiotics

Disorders of Hearing and Vestibular Function: Otitis Media

• Clinical manifestations: acute onset of otalgia, fever, irritability, otorrhea, hearing loss, evidence of middle ear inflammation, and middle ear effusion
• Symptoms: ear pain, sensation of fullness in ear, complaint of hearing loss, dizziness, decreased tympanic membrane mobility, and visible air-fluid level with or without bubble
• Risk factors: smoking in the house, prematurity, daycare attendance, unimmunized status, bottle-feeding, feeding in the supine position, being overweight or obese, family history of otitis media, being male, and sharing a bedroom
• Prevention: routine childhood vaccinations, elimination of household smoking, exclusive breast-feeding, avoiding feeding while lying down, use of xylitol, and selecting daycare facilities with small staff-to-child ratio