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455 Cards in this Set
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Physiology
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the study of specific characteristics and functions of a living organism
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Pathophysiology (3)
**Question |
1. The study of abnormalities in physiologic functioning of living beings
2. Physiology of altered health 3. Structural and functional changes in cells, tissues, and organs of the body that cause or are caused by diseas |
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Disease (3)
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1. A disruption of homeostasis
2. Disease is dynamic rather than static 3. Disease represents the sum of deviation from normal |
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Etiology
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Proposed causes or reasons for phenomena
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Pathogenesis
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Proposed mechanisms whereby a disease leads to typically oberved clinical manifestations
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Clinical Manifestations
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describe the signs and symptoms of a particular pathology
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Treatment Implications
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understanding the etiology, pathogenesis and clinical manifestations may imply treatment
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Idiopathic
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unknown cause
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Inherited Etiology
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altered or mutated genes
es: down syndrome, cystic fibrosis, sickle cell anemia |
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Congenital Etiology
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prenatal influences
occures durring pregancy |
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Matabolic Etiology
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Abnormalities in body chemestry
ex: diabetes |
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Degenerative Etiology
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Breakdown in tissue
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Neoplastic Etiology
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tumors
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Immunologic Etiology
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alteration in body protection
ex: AIDS |
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Infectious Etiology
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caused by pathogens
ex: strep throat |
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Etiology induced by physical agents
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toxic or destructive chemicals
ex: burns or hypothermia |
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Nutritional Deficiency Etiology
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deficiencies in nutrients
ex: siliac |
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Iatrogenic Etiology
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unintended medical treatment
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Phychogenic Etiology
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emotional or mental causes
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Pathogenesis
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1. How the disease process evolves-- sequence of cellular and tissue events
2. Development of a disease from the initial stimulus to the manifestations of the disease |
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Factors affecting Pathogenesis (4)
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Time
Quantity Location Morphologic Changes |
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Clinical manifestations
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describe the signs and symptoms that typically accompany a particular pathophysiologic process
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Symptom
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subjective complaint
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Sign
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manifestation that is noted by an observer
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Syndrome
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collection of different signs and symptoms that occur together
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Pathogenesis
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1. How the disease process evolves-- sequence of cellular and tissue events
2. Development of a disease from the initial stimulus to the manifestations of the disease |
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Cultural considerations
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each culture defines health and illness in a manner that reflects their experience
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Age and biological factors linked to their individuality
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a normal value for a person at one age may not be normal for a person at another age
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Factors affecting Pathogenesis (4)
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Time
Quantity Location Morphologic Changes |
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Gender differences
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relevant in both health and disease
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Situational differences
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determine whether a derivation from normal should be considered abnormal or an adaptation mechanism
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Clinical manifestations
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describe the signs and symptoms that typically accompany a particular pathophysiologic process
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Symptom
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subjective complaint
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Sign
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manifestation that is noted by an observer
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Syndrome
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collection of different signs and symptoms that occur together
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Cultural considerations
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each culture defines health and illness in a manner that reflects their experience
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Age and biological factors linked to their individuality
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a normal value for a person at one age may not be normal for a person at another age
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Gender differences
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relevant in both health and disease
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Situational differences
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determine whether a derivation from normal should be considered abnormal or an adaptation mechanism
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Sensitivity
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probability that a test will be positive when applied to a person with a particular condition
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Specificity
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probability that a test will be negative when applied to a person without a particular condition
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Validity
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degree to which a measurement reflects the true value of what it intends to measure
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Validity
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degree to which a measurement reflects the true value of what it intends to measure
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Predictive value
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extent to which a test can differentiate between presence or absence of a person's condition
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Latent period
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time between exposure of tissue to injurious agent and first appearance of signs and or symptoms
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Prodromal period:
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time during which first signs and or symptoms appear or onset of disease occurs
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Latent period also refers to a period during
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an illness when signs and symptoms temporarily become mild or silent
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Subclinical stage
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patient functions normally, disease processes are well established
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Acute clinical couse
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short lived may have severe manifestations
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Chronic clinical course
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may last months to years, sometimes following an acute course
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Exacerbation
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increase in severity, signs, or symptoms
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Remission
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decrease in severity, signs or symptoms and may indicate disease is cured
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Convalescence
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stage of recovery after a disease, injury, or surgical procedure
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Sequela
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subsequent pathologic condition resulting from an acute illness
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Epidemiology
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the study of patterns of disease in human populations
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The goals of epidemiology
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are to define a disease, identify outbreaks, addidt in the development and revaluation of treatment protocols and develop prevention strategies
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Epidemic
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disease spreads to many individuals at the same (SARS)
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Endemic
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infectious disease that is routinely found among certain populations-- local region (cholera)
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Pandemic
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affect large geographic regions-- worldwide epidemic (AIDS)
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Evidenced Based Practice
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The conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patient
Intended to direct patient care and direct research into specific health problem |
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Primary prevention
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prevention of disease by altering susceptibility
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Secondary prevention
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early detection-- screening
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Tertiary prevention
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treatment/rehab
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Homeostasis
***Question |
a state of equilibrium that is maintained by a dynamic process of feedback and regulation
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Physiologic stress
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a state of tension that can lead to disharmony or threatened homeostasis
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allostasis
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the overall process of adaptive change necessary to maintain survival and well being
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General Adaption Syndrome stages (3)
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Alarm
Resistance Exhaustion |
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Pathology occurs at
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the exhaustion stage of the GAS
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Stressors
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agents or conditions capable of producing stress
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Risk factors
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conditions or situations that increase the likelihood of encountering or experiencing a stressor
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Catecholamines
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Norepinephrine and Epinephrine
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Adrenal Cortical Steroids
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Cortisol and Aldosterone
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Endorphins and Enkephalins and Immune Cytokins
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:)
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Sex hormones
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Estrogen and testosterone
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Growth Hormone, Prolactin and Oxytocin
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:)
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Stress Syndrome **** know the Slide
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!!
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GAS Slide!!!
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Know it!!
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The neuroendocrine response to stress consists of the
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sympathetic stimulation of the adrenal medulla to secrete catcholamines and stimulation of the pituitary to secret ACTH which stimulates the adrenal cortex to secret cortisol
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Catecholamines prepare the body to
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act
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Cortisol...
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mobilizes energy
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Epinephrine exerts effects on...
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the Cardiovascular system by increasing cardiac output, increase blood flow to heart, brain and skeletal muscles and dilates airways
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Norepinephrine
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constricts blood vessels of visera and skin
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Cortisol
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mobilizes glucose, amino acids, lipids, and suppresses the immune and inflammatory function
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Adaptation
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biopsychosocial process of change in response to new or altered circumstances, internal or external in origin
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Coping
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behavioral adaptive response to a stressor using culturally based coping mechanisms
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Illness
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both physiological and psychological is a stimulus for the stress response
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**Effects of stress slide
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Physical Indicators of High Stress Levels
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Increased BP
Increased Muscle tension Tachycardia Increased respirations Diaphoresis Fatigue Tension Headache Nausea, vomiting, diarrhea Change in weight/appetite Restlessness Insomnia |
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Behavioral and Emotional Indicators of High Stress
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Anxiety, depression, alcohol abuse, change in activity patterns, exhaustion, loss of self-esteem, increased irritability, loss of motivation, decreased productivity, inability to concentrate, increased illnesses
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Stress response in children and infants is...
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brisk and timely
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Elderly persons are...
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at risk for stress related disorders, and have diminished immune function to protect themselves
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Pain is
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whatever the patient says
(subjective) |
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Pain tolerance
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is the degree of pain an individual can withstand
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Pain threshold
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is the point of pain perception
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What is the purpose of pain?
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The learn that something is harmful, pain occurs before injury occurs, pain sets limits on activity which forces inactivity which is required for healing
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Nociception
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special receptors that respond only to noxious stimuli and generate nerve impulses which the brain interprets as pain
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The pain process is
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transduction, transmission perception and modulation
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fast pathway transmission of pain
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large, myelinated A delta fibers
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slow pathway transmission of pain
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small unmyelinated C fivers
dull aching proorly localized sensations |
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Transduction
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1. Conversion of a stimulus to an action potential at the site of tissue injury
2. Chemical substances are released with cellular damage ie histamine, serotonin, and prostaglandins 3. Chemicals sensitize the primary efferent nociceptors that carry painful stimuli 4. Some analgesics work by interfering in the production of these chemicals NSAIDS |
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Transmission
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The neuronal action potential is transmitted to and through the CNA so it can be perceived (A delta and C fibers)
The impulse goes to the brain, processed in the dorsal horn and is transmitted to the brain |
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Perception
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1. Result of neural processing of pain sensations in the brain-- involves several brain structures
2. Includes an awareness and interpretation of the meaning of the sensation 3. Pain perception can be described in terms of pain threshold and pain tolerance |
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Children tend to have lower pain thresholds than do adults
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Physiologic responses may include flushing or pallor, sweating, increased heart rate, blood pressure and respiratory rate.
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Aging and perception of pain
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prevalence of pain increases with age
there may be an increase in pain threshold These changes may be caused by peripheral neuropathies and changes in the thickness of the skin May be reluctant or cognitively unable to report pain |
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Physiology of Pain:
Modulation |
1. Inhibition of nociception
2. Efferent fibers descending from the brain stem modulate or alter pain 3. Opioids such as endorphins are thought to be mediators of presynaptic inhibation 4. Many analgesics modulate pain by mimicking endogenous neuromodulators |
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Acute pain
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results from tissue injury and resolves in less than 6 months
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Chronic pain
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exists when pain lasts more than expected healing time is usually greater than 6 months
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Cancer related pain
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subcategory of chronic pain that may be associated with cancer
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Neuropathic pain
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results from tissue damage in which the nerves become damaged or dysfunctional
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ischemic pain
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results from sudden loss of blood flow to the tissues
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Referred pain
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is perceived in an area other than the actual source of the injury
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Signs and Symptoms related to pain
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1. Increased heart rate
2. increased BP 3. Increased respiratory rate 4. dilated pupils 5. Pallor and perspiration 6. Nausea and vomiting 7. Urine retention |
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Physiologic responses to pain
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1. Blood shifts from superficial vessels to muscle, heart, lungs, brain (pale and cold)
2. Bronchioles dilated to increase oxygenation 3. Decreased gastric secretions (nausea and vomiting) 4. Decreased gastric motility (constipation) 5. Increase circulating blood sugar 6. Hypomotility of the bladder and ureters |
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Acute pain symptoms
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BP changes, increased HR, diaphoresis, peripheral vasoconstriction, nausea, anxiety, increased muscle tension, increased blood glucose level
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Chronic pain
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depression, normal vital signs, difficulty sleeping and eating, localization is imprecise, exhaustion, irritability and lack of energy.
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Pain treatment modualities
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1. Interrupting peripheral transmission of pain
2. Modulating pain transmission of the spinal cord 3. Altering the perception and integration of pain |
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Atrophy
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decrease in cell size
reduces O2 consumption decrease in muscle size and lipofuscin |
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Hypertrophy
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Increase in cell size, results from increased workload, increase in functional components of cell
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Hyperplasia
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Increase in number of cells
Often occurs with hypertrophy Stimuli )hormonal, compensatory, chronic irritation) |
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Metaplasia
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Conversion of 1 adult cell type to another type, occurs in response to chronic irritation and inflammation, however conversion never oversteps their cell type boundaries
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Dysplasia
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Abnormal changes in size and shape organization of mature cells.
Not truly adaptive and strongly implicated as a precursor of cancer |
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Cellular injury
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cell unable to maintain homeostasis
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Reversible Injury
Hydrotopic Swelling |
Reduced ATP
Large pale cytoplasm Dilated endoplasmic reticulum Swollen mitochondria |
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Reversible injury
Cellular accumulations |
Lipids, glucose, protein, pigment, mineral
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Hypoxic
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Interrupts generation of ATP
Leakage of enzymes (creatine phosphokinase, lactate dehydrogenage) |
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Nutrition
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can be a cause of injury
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Chemical injury
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point of contact or metabolic problem
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Infectious of Immunologic injury
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Due to bacteria or viruses
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Physical and mechanical injury
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temperature, electrical, radiation, atmospheric, mechanical
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Aging Theories
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Error
Somatic mutration Immunologic Free radicalCross link Wear and tear |
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Necrosis
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-disruption of the permeability barrier of the plasma membrane
- generalized inflammatory response - types (coagulative, liquefactive, fat, caseous) |
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Gangrene
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Hands
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Apoptosis
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Cell suicide (governed by protein p53)
Somatic death |
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Healing by primary intention
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Inflammatory phase (reaction)
Proliferative phase (regeneration) Maturation (remodeling) |
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Healing by secondary intention
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Chronic inflammation
Granulation tissue Wound contraction |
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Healing by Tertiary Intention
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Delayed wound closure
Then Primary closure |
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Complications of Wound closures
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Hemorrhage
Infection Wound separation (dehiscence) Evisceration (organs coming out) Fistula formation (unnatural passageways) |
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Most pathologies start
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at the cellular level
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Cells adapt by undergoing changes in (3 ways)
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size, number, or type
this occurs in response to to need, once the need is gone, the adaptive response ends |
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Atrophy
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decrease or shrinkage in cellular size-- lower and more efficient level of functioning that is compatible with survival
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Causes of Atrophy
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1. Disuse
2. Denervation 3. Lack of endocrine stimulation 4. Decreased nutrition 5. Decreased nutrition 5. Ischemia, decreased blood flow 6. Persistent injury 7. Aging |
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Signs and symptoms of Atrophy
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1. Decrease in muscle size
2. Ischemic changes 3. Yellow brown intracellular pigment called lipofuscin (brown atrophy) |
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Hypertrophy
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Increase in cell size-- increase in amount of functioning tissue mass
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Hypertrophy Causes
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results from increase work load imposed on an organ or body part
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Examples of Hypertrophy
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1. Mucle mass due to exercise
2. Heart (left ventricular hypertrophy) due to ^ workload to hypertension 3. Kidney after 1 kidney removed 4. Uterus/mammary glands in response to pregnancy 5. Liver in response to bodily toxins |
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Hyperplasia
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Increase in number of cells in organ-- occurs in cells capable of miotic division (epidermis, intestinal, epithelium, and glandular tissue)
Often occurs with hypertrophy |
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Hyperplasia causes
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hormonal, compensatory, chronic irritation
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Metaplasia
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1. Conversion of 1 adult cell type to another adult cell type
2. Occurs in response to chronic irritation and inflammation 3. Conversion never oversteps the boundaries of the primary group of tissue |
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Dsplasia
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1. Abnormal changes in size, shape and organization of mature cells
2. Not truly adaptive 3. Generally a precursor to cancer |
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Cellular injury
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Occurs when cell unable to maintain homeostasis
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Degree of cellular injury related to
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1. intensity and duration of injury
2. Type of cell involved 3. Blood supply of cells 4. Nutritional status 5. Previous reserves and state of functioning |
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Reversible injury: Hydropic swelling
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reduced ATP-- acute cellular swelling due to failure of energy dependent Na-K membrane pump
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Intracellular accumulation: Excess accumulations of substances may cause cellular injury because
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a. substances are toxic
b. they provoke an immune response c. they take up too much cellular space |
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Accumulation of normal intracellular substances
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a. Lipids: accumulation in liver, blood vessels, kidneys, heart, and in some diseases(Tay Sachs) enzymes for metabolism are absent and lipids accumulate in neurological tissue
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Accumulations of Glycogen and Glucose
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Diabetes ensues and kidneys reabsorb excess filtered glucose and store it as glycogen-- changes in renal and nerve cells.
Neurons absorb glucose because they don't need insulin for absorption |
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Accumulations of proteins
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misfolded proteins that have been damaged by UV, heat, free radical injury etc
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Pigment excess example
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tanned skin
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Accumulations of mineral excess
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in coal dust, silica, iron, lead and silver
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Etiology of cellular injury
Ischemic and hypoxic injury |
Hypoxia causes power failure in cells
Interrupts oxidative metabolism and generation of ATP often slow to develop Causes are: -Inadequate amount of O2 in air -respiratory disease -anemia -edema -inability of cells to use O2 |
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Ischemic and Hypoxic Symptoms
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1. Hydrotropic swelling
2. Leakage of intracellular enzymes through permeable cell membrane is used as clinical indicator of cellular death Lactic acidosis: due to the breakdown of cellular store of glycogen |
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Etiology of cellular injury
Nutritional Injury |
Excess and deficiency can predispose a cell to injury
Iron deficiency anemia, scurvy, beriberi, pellagra |
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Etiology of cellular injury
Chemical Injury |
Chemicals injure cell membranes and other cell structures, block enzymatic pathways, coagulate cell proteins and disrupt the osmotic and ionic balance of cells
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Etiology of cellular injury
Infectious or Immunologic Injury |
1. Biological agents different in that they can replicate and continue to produce their injurious effects
2. Disease producing potential of microorg depends on ability to invade and destroy cells, produce toxins and produce damaging hypersensitive reaction |
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Physical and mechanical injuries
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Temperature
Electrical Radiation Atmospheric Mechanical |
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Cellular aging due to
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DNA damage
Reduced proliferative capacity of stem cells (End caps of chromocome (telomeres) shorten with each cell division and telomerase rebuilds telomere, therefore progressive loss of telomerage gene with aging may lead to reduced proliferative capacity) Free radical theory (cumulative and progressive damage to cell structures from free oxygen radicals) |
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Cellular Death
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Necrosis
1. Caused by external injury 2. Disruption of the permeability barrier of the plasma membrane 3. Usually results in death in a localized area with a systemic response |
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Coagulative Cell Death
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Calcium accumulates in dead cells due to failure of ATP pump
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LIquefactive Cell Death
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Dissolution of dead cells occurs quickly
Abscess of cyst Brain or bacterial infection |
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Fat Cell Death
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death of adipose tissue due to trauma or pancreatitis
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Caseous (encapsulated)
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lung tissue damaged by TB; white, clumpy cheese
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Gangrene
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Hypoxic to the max
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Apoptosis
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Cell suicide governed by protein p52 (which increases with cellular DNA damage) and might be a precursor to cancer
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Signals of Apoptosis
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1. Withdraw of survival signals from other cells
2. Extracellular signals bind to cell and trigger "death cascade" |
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Intrinsic pathways of Apoptosis
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Governed by protein p53, which increases with cellular DNA damage
Increase of p53 leads to apoptosis |
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In some cancers
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the monitoring system is evaded
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Somatic death
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death of entire organism
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Wound healing requirements
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Nutrition (protein, carbohydrates, fat and minerals)
Blood flow Inflammatory and immune responses |
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Primary intention
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Little loss of tissue, wound edges approximate
1. Inflammation - Hemostasis - Vasodilation due to secretion of histamine from damaged cells - Leukocytes - Fibroblasts- synthesis of collagen - Epithelial cells move in 2. Proliferative phase - New blood vessels formed - Filling in wound with new granulation tissue - Closing of top of wound by epithelization 3. Maturation - collagen scar continues to reorganize and gain strength - usually has fewer pigmented cells than normal skin |
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Secondary intention
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occurs when tissue loss is extensive (burn, pressure ulcer, severe laceration)
1. Inflammation is chronic 2. Tissue defects filled with fragile granulation tissue rather than collagen 3. Wound contraction |
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Third intention
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Delayed wound closure
Generally the wound was infected, so you cant suture it because it might lead to sepsis. You have to suture once its clean. |
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Primary intention simplified
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Inflammatory (reaction)
Proliferative phase (regeneration) Maturation (remodeling) |
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Complications of injury
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Hemorrhage, Infection, wound separation, fistula formation
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Generally malignant growth
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can kill and benign cannot.
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Benign neoplasia
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do not invade other tissues, and more closely resemble cell of origin
it is easier to cure, slow growth rate, good prognosis, cells are well differenciated (you can tell what type) and encapsulated. they are named according to what tissue they are involved in, they don't metastisize |
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Malignant neoplasia
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Second most common cause of death in US, leading cause of death in those <80
Overall 5 year survival rate is 62%-- some much lower/higher Has undiferentiated cells, invade local tissue and overrun it, grows rapidly, migrates form the site of origin, not capsulated, highly proliferative. |
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Etiology of neoplasia with a Genetic Basis (cancer)
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Cancer cause small number of mutations in a single cell, this takes place over time
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Etiology of neoplasia with a Genetic Basis (Tumor Suppressor genes)
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Normally occurring enes that work to turn off cell division
Two genes in each pair, if a damaged one is inherited, only required damage of the remainder to increase the risk |
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Etiology of neoplasia with a Genetic Basis (Rb Gene-retinoblastoma)
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Hereditary or sporadic
Autosomal dominate on Chromosome 13 |
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P53 gene
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More than half of all human tumors lack p53
Only accumulates after DNA damage |
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BRCA genes
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BRCA 1 (Chromosome 17)
BRCA 2 (Chromosome 13) Only 15% of all cases of breast cancer due to inherited mutation |
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Oncogenes
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Protooncogenes exist in cells to turn on or maintain cell division
When permanently activated, they become oncogenes (uncontrolled cell division) Activation comes from Viruses or retroviruses or a mutagenic event of if DNA sequences are damaged or lost and lastly amplification |
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Effect of oncogenes
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1. Autocrine growth factors produced
2. Growth factor receptors 3. Cytoplasm signaling pathway 4. Abnormal transcription factors |
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Mutation of caretaker genes
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encode protein that maintain maintain integrity of genome -- DNA repair genes
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Carcinogenesis
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Initiation, Promotion, Progression
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Initiation
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results when a carcinogen, such as UV radiation, is applied to the cell
1. carcinogen may enter cell and irreversibly bind to DNA 2. DNA repair is possible but if it does not occur before before cell division, cell will replicate into daughter cells, each with the same genetic mutation |
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There can be different kinds of carcinogens, two examples are
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chemical and physical
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Promotion
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Mutant cell proliferates:
1. May involve activation of another oncogene or inactivation of a tumor suppressor gene 2. Nutritional factors or infection may provide stimulus for proliferation 3. Hormones - Estrogen: Increase of menstrual cycles, higher risk of breast, ovarian, or uterine cancer. Also, early menarche, late first pregnancy, lack of breast feeding, late menopause increase risk - Testosterone: prostate cancer 4. Failure of the immune system to intercept |
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Progression
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Characterize by increase growth rate and invasiveness of tumor. Tumors can even produce their own GH
Lack of contact inhibition-- will invade territory that is not their own Cells metastasize (spread to distant parts of the body) spreads via vascular system, lymphatic system and process of implantation (implant cells on serous cavities-- peritoneal and pleural) |
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Metastasis characteristics
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1. retain many of characteristics of primary site
2. site of hematologic spread is usually related to vascular drainage of the primary tumor 3. Some tumors tend to "home" to specific target organs (tropism) that can provide substances such as growth factors or hormones that they need for survival |
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The type of cell tell you what type of treatment
***question |
tumor markers tell what type of cell and amount of cells involved, this lets us see how well chemotherapy is working
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Angiogenesis
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Tumors can not enlarge more than 2mm in dimeter unless they grow new blood vessels
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Histological Analysis Classification
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Grade I-IV
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Grade I
|
cells slightly different from normal cells and well differentiated
|
|
|
Grade II
|
cells are more abnormal and moderately differentiated
|
|
|
Grade III
|
cells are very abnormal (severe dysplasia) and poorly differentiated
|
|
|
Grade IV
|
Cells are immature and primitive (anaplasia) and undifferentiated, cell of origin is difficult to determine
|
|
|
Extent of disease classification
|
Stages 0-4
|
|
|
Stage 0:
|
Cancer in situ
|
|
|
Stage 1:
|
Cells are more abnormal and moderately differentiated
|
|
|
Stage 2:
|
Limited local spread
|
|
|
Stage 3:
|
Extensive local and regional spread
|
|
|
Stage 4:
|
Metastasis
|
|
|
Carcinomas
|
cancer of skin and glands and MM
|
|
|
Sarcomas
|
cancer of connective tissue muscle bone and fate
|
|
|
Warning signs of cancer
|
C hange in bowel or bladder habits
A sore that does not heal U nusual bleeding or discharge from any body orifice T hickening or lump in the breast or elsewhere I ndigestion or difficulty swallowing O bvious change in a wart or mole N agging cough or hoarseness |
|
|
Later signs of Cancer
|
1. Pain
2. Cachexia 3. Deficits in immune system competence 4. Bone marrow suppression 5. Loss of function of involved organ 6. obstruction 7. Paraneoplastic symdromes |
|
|
Diagnostic procedures
|
blood studies are tumor markers. Substances that are secreted by tumors that are found in blood-- not definitive but used more to monitor therapy
|
|
|
Other diagnostic procedures
|
X ray, CT, ultrasound, bone scanning, MRI, PET scanning, Endoscopic, Biopsy
|
|
|
Biopsy
*****question |
the only definitive diagnosis for cancer. Can tell staging and histological and grade information and therefore to predict treatment
|
|
|
Cancer treatments
|
Surgery, Radiation, Chemotherapy, Immunotherapy (or gene therapy-- suppress the oncogene)
|
|
|
Risk factors
|
Smoking, sunlight, alcohol, smokeless tobacco, estrogen, radiation, occupational hazards (nickel, cromate, asbestos, vinyl chloride) high fat diet--obesity
|
|
|
Epithelial barriers
|
block foreign material entering the body
Provide multilayer protection Dry surface does not promote organism growth Sloughing of skin/mucosal layer aids in microorganism removal |
|
|
Stress associated with increased secretion of corticosteriods
|
is believed to depress the immune system
|
|
|
Exogenous steroids and other immunosuppressive therapies
|
also depress it
|
|
|
Types of Pathogenic Organisms
|
bacteria, viruses, fungi, parasites
|
|
|
Bacteria
|
Single cell organisms that do not require living cells for survival
|
|
|
Bacteria Clinical Manifestations
|
fever, body aches, regional lymph node enlargement and site specific manifestations ie cough, earache, sore throat
|
|
|
Bacterial infections growth
|
Growth depends on body's immune system function and ability to resist body defenses
May produce toxins that cause damage to cells and tissues Complement proteins may be activated by contact with bacteria |
|
|
Bacteria can be treated with
|
antibiotics
|
|
|
Viruses
|
cause transient illnesses like colds and flus
they are intracellular pathogens Either DNA or RNA Viruses stimulate the immune system's antibody activation |
|
|
Viral clinical manifestations
|
low grade fever and site specific manifestations
|
|
|
Viral Infections
|
Viruses can be local or systemic, damage or kill
|
|
|
Fungi
|
Can be superficial, subQ or systemic
Grow in two form: yeasts and molds Produce disease by generating toxic substances, individuals may become sensitized to antigens resulting in an allergic reaction or actively grow on a human host Infections caused by fungi are called mycotic Deep fungal infections can spread systemically and invade tissues, destroying vital organs in immunocompromised hosts Superficial infections involve the skin, hair and nails. Fungal species that are confined to superficial layers of the human skin are known as dermatophytes. Clinical manifestations include: itching, redness of skin, vaginal discharge etc. |
|
|
Infections caused by fungi
***** |
Mycotic
|
|
|
Parasite examples:
|
Protozoa, helminths (worms), arthropods
|
|
|
Parasites can live
|
on or in the body during some part of their life
|
|
|
Clinical manifestations of parasites include
|
depending on the area, skin (itching and rash) and GI tract (diarrhea)
|
|
|
Resident flora
|
occupy certain environment on the host
|
|
|
Transient flora
|
reside temporarily and may be harmless or potentially harmful
|
|
|
Opportunistic flora
**** |
normal flora become pathogenic when the immune system is compromised
|
|
|
Virulent
|
when a microorganism is capable of consistently causing disease in all infected hosts
|
|
|
Infectious disease
|
occurs when pathogens enter a host and causes signs and symptoms of illness
|
|
|
Symptoms of Systemic Infection
|
malaise
weakness headache anorexia acute inflammatory reactions |
|
|
Enteropathic bacteria
|
elicit gastrointestinal disease by a variety of mechanisms:
Growing on food. Examples are cholera, ecoli, shingles, salmonella |
|
|
Dysentery
|
very watery diarrhea (with blood) from ulcer-like diseases
|
|
|
Typhoid fever passes through
|
Peyer's patches through the GI tract into the lymph nodes
|
|
|
Bioterrorism
*** |
the deliberate use of microbial agents and their toxins to impact the health of a group of people
|
|
|
Category A Diseases/Agents
|
the highest risk agents and can be readily disseminated or transmitted from person to person, can cause high mortality with potential for major public health impact
|
|
|
The function of the immune system
*** |
is to protect the host from invasion of foreign organisms by distinguishing self from nonself
|
|
|
The major lymphocytes involved in protecting the body against infections and tumor growth are
|
B and T cells
|
|
|
The primary lymphoid organs are the
|
thymus and bone marrow
|
|
|
Leukocytes
|
neutrophils, eosinophils, basophils and mast cells, monocytes and macrophages
|
|
|
Lymphocytes
|
natural killer cells, T lymphocytes (cell mediated) and B lymphocytes (secrete antibodies and immunoglobulins
|
|
|
Chemical mediators
|
Complement (enhances inflammation)
Kinin (vasodilator) Cytokins (stimulate surface receptors) Clotting factors (coagulation) |
|
|
Lymphoid system
Primary organs |
Bone marrow
Thymus gland |
|
|
Lymphocytes produced from stem cells
|
T lymphocytes migrate to thymus to develop
B cells and NK cells stay in marrow |
|
|
Secondary Lymphoid Organs
|
Lymph nodes
Spleen Tonsils Peyer's Patches |
|
|
Antigens
|
substances recognized as foreign or non self and provoke an immune response
|
|
|
Humoral Immune Response
(Antibody mediated Immunity) |
Defined as an antibody-mediated immune responses produced by B lymphocytes
Antibodies are an immune or protective protein evoked by an antigen |
|
|
Antibody Mediated Responses
|
Phagocytosis
Precipitation Neutralization Lysis of antigen membrane Agglutination Opsonization |
|
|
Cell Mediated Immune Responses
|
Defined as immune system response to antigens that do not evoke the antigen mediated response because they live inside the body's cells
Antigen activated T cells T cells are antigen specific |
|
|
***Know Neutrophils, Basophils, Eosinophils, Monocytes, Lymphocytes
|
****
|
|
|
Active Immunity
|
occurs when the body produces antibodies against specific antigens
Memory cells produce an immediate response on exposure to the antigen and provide long term immunity Can be naturally acquired resulting from contact or artificially acquired through immunizations or vaccinations |
|
|
Passive Immunity
|
Produces temporary protection against disease producing antigens
naturally acquired passive immunity is provided by the transfer of maternal antibodies via the placenta and breast milk to the infant Artificially acquired passive immunity is provided by immune globulins and serums |
|
|
Inflammation
|
occurs when cells are injured
Rapid and non specific protective response to cellular injury from any cause Protective mechanism that begins the healing process |
|
|
IGG
|
most common
crosses the placenta |
|
|
IGM
|
produced first
released upon exposure to antigen |
|
|
IGA
|
Saliva, mucus membranes, GI, semen
|
|
|
IGE
|
release in allergic reactions
|
|
|
IGD
|
differentiation of B cells
|
|
|
Inflammatory process
|
Increase vascular permeability
Recruitment and emigration of leukocytes Phagocytosis of antigens |
|
|
Purpose of Inflammatory response
|
to neutralize and destroy invading agents
Limit the spread of harmful agents Prepare damaged tissue for healing |
|
|
Cardinal signs of Inflammation
|
Redness
Swelling Heat Pain Loss of function |
|
|
Stimuli for acute Inflammation
|
Infections (bacterial, viral, parasitic) and microbial toxins
Trauma (blunt and penetrating) Physical and chemical agents (thermal injury, burns or frostbite, irradiation) Tissue necrosis Foreign bodies (splinters, dirt, sutures) Immune reactions (also called hypersensitivity reactions) |
|
|
Inflammatory Exudates
|
Transport leukocytes and antibodies
Dilute toxins and irritating substances Transport nutrients for tissue repair |
|
|
Types of Inflammatory Exudates
|
Serous exudate (watery protein--blister)
Serosanguineous exudate (serous exudate with blood) Fibrinous exudate-- sticky, thick, scabs Purulent exudate Hemorrhagic exudate (breakdown and leakage of RBCs) |
|
|
Systemic Effects of Inflammation
|
Fever
Neutrophilia (increase of neutrophils) Lethargy Muscle catabolism Increased acute phase protein levels Increased Erythrocyte Sedimentation Rate ESR |
|
|
Beneficial Effects of Inflammation
|
Dilution of Toxins
Entry of antibodies Drug transport Fibrin formation Delivery of nutrients and oxygen Stimulation of immune response |
|
|
Dilution of toxins
|
Dilution of toxins such as those produced by bacteria, allows them to be carried away in lymphatics
|
|
|
Entry of antibodies
|
increase vascular permeability allows antibodies to enter the extravascular space, where they may lead either to lysis of microorganisms
|
|
|
Drug transport
|
the fluid carries wit it therapeutic drugs such as antibiotics to the site where bacteria are multiplying
|
|
|
Fibrin formation
|
Fibrin formation from exuded fibrinogen may impede the movement of micro-organisms, trapping them and so facilitating phagocytosis
|
|
|
Delivery of nutrients and oxygen
|
which is essential for cells such as neutrophils which have high metabolic activity, is aided by increased fluid flow through the area
|
|
|
Stimulation of immune response
|
the drainage of this fluid exudate into the lymphatics allows particulate and soluble antigens to reach the local lymph nodes where they may stimulate the immune response
|
|
|
Harmful effects of Inflammation
|
Digestion of normal tissues: enzymes such as collagenases and proteases may digest normal tissues, resulting in their destruction
Swelling: the swelling of acutely inflamed tissues may be harmful: for example, the swelling of the epiglottis in acute epiglottitis in children de to Haemophilus influenzae infection may obstruct the airway, resulting in death. Inappropriate inflammatory response |
|
|
test
|
test
|
|
|
Histatmine
**** |
this is the best known chemical mediator in acute inflammationIt causes vascular dilation and the immediate transient phase of increased vascular permeability. It is stored in mast cells, basophils, and eosinophil leukocytes and platelets
|
|
|
Lysosomal compounds
|
these are released from neutrophils and include cationic proteins, which may increase vascular permeability and neutral proteases, which may activate complement
|
|
|
Prostaglandins
|
Some prostaglandins potentiate the increase in vascular permeability caused by other compounds. part of the anti-inflammatory activity of drugs such as aspirin and the non steroidal anti inflammatory durgs is attributable to inhibition of one of the enzymes invloved in prostaglandin synthesis
|
|
|
Leukotrienes
|
These are also synthesised from arachidonic acid, esspecially in neutrophls and appear to have vasoactive properties.
|
|
|
5-hydroxytryptamine (serotonin)
|
this is present in high concentration in mast cells and platelets. it is a potent vasoconstrictor
|
|
|
Lymphokines
|
this family of chemical messengers released by lymphocytes. Apart from their major role in type IV hypersensitivity, lymphokines may also have vasoactive or chemotactic properties
|
|
|
Autoimmunity
|
an individual's immune system recognizes its own cells as foreign and mount san immune response that injures self tissues
|
|
|
SLE
|
Systemic Lupus Erythematosus
Autoimmune |
|
|
SLE characteristics
|
CHRONIC
injury to the skin, joints, kidney and serosal membranes Chronic inflammation, rheumatic, autoimmune disease, characterized by remissions and exacerbations Type III hypersensitivity (antigen-antibody complexes are deposited in tissues) |
|
|
SLE incidence
|
predominantly in women of childbearing age and more severe in African Americans
|
|
|
SLE pathology
|
body produces auto antibodies which combine with antigens to form immune complexes
accumulation of immune complexes within connective tissue triggers the inflammatory response chronic inflammation destroys the connective tissue |
|
|
SLE clinical manifestations
|
fever
malaise/fatigue weakness weight loss polyarthralgia **butterfly rash renal failure seizures infections usually a positive ANA |
|
|
Malar rash
|
= butterfly rash
|
|
|
SLU can be associated with
|
endocarditits
|
|
|
Life expectancy with SLE
|
10-15 years
|
|
|
Type I Hypersensitivity
|
The immune response release vasoactive and spasmogenic substances that act on vessels and smooth muscle and pro-inflammatory cytokines that recruit inflammatory cells
IgE mediated Produces an immediate reaction Local or systemic Occurs when an allergen interacts with IGE bound to mast cells and basophils |
|
|
Type I Hypersensitivity examples
|
Allergic asthma, hay fever, allergic conjunctivitis, hives, anaphylactic
|
|
|
Type I Hypersensitivity clinical manifestations
|
vasodilation, hypotension, urticaria, bronchoconstriction
|
|
|
Type II Hypersensitivity
|
secreted antibodies participate directly in injury to cells by promoting their phagocytosis or lysis and injury to tissues by inducing inflammation
Characterized by IgG or IgM antibodies Occurs on cell surfaces Lysis occurs |
|
|
Type II Hypersensitivity examples
|
hemolytic transfusion reaction, incompatible blood type, drug reaction
|
|
|
Type III Hypersensitivity
|
Antibodies bind antigens and then introduce inflammation directly or by activating complement. Results from the formation of IgG or IgM antibody antigen complexes that circulate in the blood. Complexes then adhere to the walls of the vessels and cause inflammation and destruction
|
|
|
Type III Hypersensitivity examples
|
serum sickness and auto immune conditions
|
|
|
Type IV Hypersensitivity
|
Sensitized T lymphocytes are the cause of the cellular and tissue injury delayed reactions.
Result from exaggerated interaction between the antigen and normal cell mediated mechanisms |
|
|
Type IV Hypersensitivity examples
|
contact dermatitis, transplant reactions (graft vs host), MS?
|
|
|
HIV/AIDS
|
is the most common immunodeficiency disorder worldwide
it is one of the greatest <i>epidemics</i> in human history |
|
|
AIDS is the consequence of
|
a chronic retroviral infection that produces severe, life threatening CD4 helper T lymphocyte dysfunction, opportunistic infections and and malignancy
|
|
|
HIV tests
|
Western blot
ELISA |
|
|
AIDS test
|
CD4 count below 200 cells/ml or the presence of an AIDS indicatory condition: PCP, TB invasive cervical cancer, Kaposi's sarcoma and others
|
|
|
HIV I
|
From central Africa
Causative agent of most AIDS cases found in central Africa |
|
|
HIV II
|
From West Africa and found there
|
|
|
HIV etiology
|
HIV gains access to CD4 cells by attaching to the CD4 receptor on the cell surface
|
|
|
Transmission of HIV
*** |
Sexually
Parenteral through blood Perinatal in utero, delivery and breast milk |
|
|
Transmission of HIV NOT through
|
urine, saliva, tears, cerebrospinal fluid, and feces
|
|
|
HIV and AIDS Pathophysiology
|
The key element in HIV infection is the high level of virion production and the high level of CD4 + cell death
|
|
|
Once in the cell, HIV
|
converts RNA to viral DNA and then replicates during normal cell processes
The hallmark of AIDS is a decrease in CD4 cells |
|
|
Hemophiliacs
|
and HIV?
|
|
|
HIV effect of Immune cells at a cellular level
|
Hallmark of HIV infection: decrease in CD4 T helper/inducer lymphocytes
Macrophages become more functionally impaired as infection progresses and also contribute to T cell decline by increasing CD4 cell death B cell responsiveness decreases because of dependence on T-cell helper cytokines The virus may be dormant or become activated-- but antibodies are produced between 6 weeks and 6 months of infection Seroconversion takes 6-12 weeks In later stages opportunistic infections occur |
|
|
HIV and AIDS Clinical Manifestations
|
All body systems are affected by HIV
Early infection is characterized by fever, chills, weakness, sore throat, fatigue, and N&V Gastrointestinal/malnutrition/diarrhea Pulmonary--PCP Mucocutaneous/candidiasis (white in throat) Gynecologic/PID Neurological-- neuropathy, encephalopathy Opportunistic infections Positive ELISA and Western blot test |
|
|
Diagnostic testing for HIV
|
ELISA (enyme-linked immunosorbent assay)
-Positive for HIV antibodies if blood or oral mucosal transudate of an infected person reacts with the surface antigen of killed HIV virus Highly sensitive and specific Must be performed with both HIV1 and HIV2 viral antigens |
|
|
Diagnostic testing for HIV
|
Western blot
-Used when ELISA test is positive -Uses electrophoresis Identifies specific antibodies against the HIV protein antigen -Specificity >99.9 -Patient must wait 1-2 wk for confirmation |
|
|
Diagnostic Testing for HIV
|
OraQuick Rapid HIV1
-New rapid fingerstick-based HIV assay -Test results can be obtained in 20 minutes -Positive results must be confirmed by Western blot -False-negative results can occur |
|
|
The best method to test neonates for HIV
|
culture virus from blood and peripheral tissue
|
|
|
Genetic and Developmental Disorders
|
Starts now.
I have too much to do. |
|
|
Congenital disorders
|
present at birth (genetic or environmental cause)
|
|
|
Congenital malformations
|
associated with structural defects due to errors in fetal development
mostly genetic cause, sometimes environmental |
|
|
Chromosomes
|
structures in the nucleus that contain DNA which transmits genetic information
|
|
|
Gene
|
DNA, the basic block of heredity located at a particular site on the chromosome
|
|
|
Allelle
|
one of two or more different genes that contain specific inheritable characteristics (eye color) and that occupy positions on paired chromosomes-- one gene from each parent
|
|
|
Phenotype
|
outwardly apparent physical and biochemical attributes
|
|
|
Genotype
|
unique genetic makeup
|
|
|
Karyotype
|
display of human chromosomes based on length and location of the centromere
|
|
|
DNA mutation
|
inherited alteration of genetic material-- permanent change in DNA structure. Rare. Potential mutagens are radiation, chemicals, and viruses
Single stranded breasks are easily repaired Double stranded breaks may result in permanent loss of genetic information at break point |
|
|
Single gene (menelian) disorders
|
are due to DNA mutation that codes for a particular protein
|
|
|
Chromosome structures
|
are mutated through loss, gain or translocation of segments
|
|
|
Genetic Disorders
|
are caused by single genes usually follow autosomal dominant, autosomal recessive or x linked recessive models of inheritance
Apparent at birth or in later life majority inherited from parents, some from fetal development mutations |
|
|
Four groups of genetic disorders
|
1. Chromosomal aberrations
2. Mendeliam single gene disorders 3. Multifactorial/polygenic disorders 4. single gene but doesn't follow mendelian pattern |
|
|
Chromosomal abnormalities
|
generally due to abnormal number of chromosomes or alterations to the structure of one or more
Usually a result of separation or crossing over errors during meiosis or mitosis Leading known cause of mental retardation and miscarriage |
|
|
Abnormal Cromosome Structure
|
Usually due to breakage and loss or rearrangement of chromosome pieces during meiosis or mitosis
|
|
|
Meiosis
|
crossing over errors: chromosome portions lost, attached upside down, or attached to wrong chromosome
|
|
|
Mitosis
|
Opportunities for chromosomal breakage and impairment
|
|
|
Chromosomal rearrangements:
Translocation |
Exchange of DNA pieces between non-homologous chromosomes
Reciprocal translocation: no lost genetic material, sometimes no symptoms, increased risk of producing abnormal gametes |
|
|
Chromosomal rearrangements:
Inversion |
Reversal of gene order
No net loss/gain of genetic material Often no significance to individual, but may affect offspring |
|
|
Chromosomal rearrangements:
Deletion |
Loss of a portion of chromosomal material
Caused by break in arm of single chromosome Results in DNa fragment with no centromere Piece lost in next cell division Associated with some forms of cancer Deletions at both ends may form a ring chromosome |
|
|
Chromosomal rearrangements:
Duplication |
Presence of a repeat gene or gene sequence-- results in extra copies of a portion of DNA
Less severe consequences |
|
|
Trisomy 21
|
Occurs when nondisjunction of chromosome 21 occurs at meiosis
Extra 21st chromosome Most common chromosomal disorder and leading cause of mental retardation Protruding tongue, low set ears, epicanthal folds, poor muscle tone, short stature, congenital; heart deformities, increased susceptibility to respiratory infections, leukemia, Alzheimer's Majority of fetuses either stillborn or aborted |
|
|
Sex chromosome disorders: Klinefelter Syndrome
|
Common genetic disease of the sex chromosomes
Usually 1 extra X chrom Lack of secondary sex characteristics during puberty Symptoms: -Lack of testosterone -Testicular atrophy, infertility -Feminine hair distribution -Tall stature, long arms/legs -High pitched voice -Impaired intelligence Testosterone therapy usually indicated |
|
|
Sex chromosome Disorders:
Turner's Syndrome |
Monosomy X: 1 normal x, no y chromosome
Female phenotype with no ovaries Second X chromosome missing or structurally abnormal, usually due to father's advanced age Short stature, webbed neck, fibrous ovaries, sterility, amenorrhea, wide chest, congenital heart defects |
|
|
Mendelian single gene disorders
|
Result from alterations of mutations of single genes
Affected genes may code for abnormal enzymes, structural or regulatory proteins Pedigree may help trace transmission though the family Classified according to location of defective gene and mode of transmission (autosomal dominant, autosomal recessive, sex-linked) |
|
|
Autosomal dominant disorders
|
due to mutation of a specific autosomal gene
-males/females equally affected -usually 1 affected parent -unaffected individuals do not transmit disease |
|
|
Autosomal dominant disorder: Marfan Syndrome
|
Connective tissue disorder
Typically tall, slender, long, thin arms/legs, long, thin fingers Cardiovascular lesions most threatening Aorta tends to be weak, susceptible to dilation/rupture Traced to mutations in fibrillin 1 gene on chromosome 15 |
|
|
Autosomal Recessive Disorders
|
Mutation of autosomal recessive gene
Male/females equally affected Usually not apparent in affected individuals; both parents carriers of mutant recessive gene Unaffected infividuals may transmit to offspring: two carriers have 1:4 chance of having affected offspring and 2:4 chance of having carrier offspring |
|
|
Autosomal Recessive disorders
|
Albinism
Phenylketonuria (inborn error of metabolism) Cystic fibrosis (most common) |
|
|
Sex linked Disorders
|
Mutation of sex chromosome (almost always X)
nearly all X linked disorders are recessive Females express disease when both Xs are bad, males only need 1 Hemophilia A example!!! |
|
|
Nonmendelian single gene disorders
|
caused by long triplet repeat mutations, such as fragile X syndrome
due to mitochondrial DNA mutations associated with genomic imprinting |
|
|
Nonmendelian Single gene disorders Triplet repeat mutations
|
Fragile X syndrome
Premutation: possible to have an intermediate number of inherited repeats which increase the risk of mutation Maes more severely affected |
|
|
Multifactorial (Polygenic) Disorders
|
Ver common
Result from the interaction of multiple genes "run in families" Though to be produced by an interaction of many genes Also present range of severity Difficult to predict based on family history Very common (high blood pressure, cancer, diabetes) Hight, weight, intelligence |
|
|
Environmentally induced Congenital disorders
|
Errors in fetal development that result in congenital malformations
Teratology: study of developmental anomalies Numerous environmental influences (teratogens**) may adversely affect developing fetus-- chemicals, radiation, viral infections Susceptibility depends on amount of exposure |
|
|
Environmentally Induced Congenital Disorders
Periods of Fetal Vulnerability |
Before 3rd gestational week: teratogen exposure either damages very few cells or so many that embryo cannot survive
3rd to 9th week: embryo very susceptible to teratogenesis (esspecially 4th and 5th weeks during organ development) After 3rd month, teratogens affect growth or injury to already formed organs |
|
|
Cerebral palsy
|
placenta previa>bleeding> decrease in O2 for baby
Placenta obrupsia> bleeding into amniotic fluid |
|
|
Prenatal diagnosis and counseling
|
>34 years momma
Chromosomal disorder in previous pregnancy Known family hx of x-linked disorders Known family hx of inborn errors of metabolism (PKU) Neural tube anomalies in previous pregnancy Known carrier for recessive genetic disorder |
|
|
Prenatal diagnosis and counseling tests
|
ultrasound
amniocentesis chronic villus sampling embryoscopy Treat genetic disease by replacing defective gene with healthy gene Recombinant DNA technology to use genetic engineering in which there is laboratory alteration of genes |
|
|
Alterations in Endocrine Control
|
This is the last section.
You are almost there. This is possible. Its worth it. Don't feel bad. |
|
|
Endocrinology
|
the study of communication and control within a living organism by means of chemical messengers that are synthesized in whole or in part by that organism. Intercellular communication network
|
|
|
Hormones
|
chemical messengers that travel from cell to cell through the bloodstream and extracellular fluid
|
|
|
Various feedback signaling systems provide
|
the hormonal homeostasis characteristic of virtually all endocrine systems
|
|
|
The endocrine system regulates
|
the stress response
growth and development fluid and electrolyte balance reproduction |
|
|
The hypothalamus
|
secretes hormones which make other endocrine glands secrete hormones
|
|
|
The pituitary gland is regulated by three interacting elements
|
1. hypothalamic inputs-- releasing factors
2. feedback effects of circulating hormones 3. secretions of the pituitary itself |
|
|
Classification of endocrine disorders
*** |
Primary-- due to dysfunction of the target gland
Secondary-- due to dysfunction of the pituitary gland |
|
|
Hyperfunction
|
Etiology
-Autoimmune stimulation -Secreting tumors -Idiopathic Treatment -Surgical removal -Blocking drugs -Irradiation |
|
|
Hypofunction
|
Etiology
-Autoimmune inhibition -Nonsecreting tumors -Surgical removal -Ischemia, infarct -Receptor defects Treatment -Hormone therapy |
|
|
Aging and Endocrine Dysfunction
|
Decreased target organ sensitivity
Decreased levels Decreased production and clearance Increased levels Results in variable hormone activity responsiveness, secretion and target organ sensitivity |
|
|
Regulation of non pituitary systems
|
Aldosterone-->fluid retention and vasoconstriction
Parathyroid system-->increased calcium Insulin--> decreased glucose |
|
|
Growth Hormone
|
Necessary for growth
Regulates cell division and synthesis of protein Exerts metabolic effects on endocrine organs, skin, skeletal muscle, cardiac muscle and connective tissue Anabolic hormone that increases protein synthesis and fat utilization |
|
|
Increased release of GH
|
-decreased glucose
-decreased free fatty acids -fasting -exercise -stress Alpha 1 agonists |
|
|
Decrease release of GH
|
increased glucose
increased Free Fatty Acids obesity aging somatomedin ssomatostatin Beta agonists |
|
|
Too much GH
|
in children: tall stature
in adults: acromegaly |
|
|
Too little GH
|
in children: short stature
in adults: decreased muscle?? |
|
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Hyperpituitarism
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giantism and acromegaly
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Hypopituitarism
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dwarfism
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hypogonadism
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is often associated with giantism and leads to delayed epiphyseal closure
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Acromegaly clinical manifestations
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large hands and feet
protrusion of lower jaw course facial features signs of osteoporosis change in hand, shoe and glove size hypertension arthritis CAD/CHF DM enlarged adrenal gland amenorrhea headache sweating weakness hypertension |
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somatomedin
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pre-growth hormone
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GH deficiency clinical manifestations
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Hypoglycemia
Growth below 3rd percentile Dental eruption delayed Irregular setting of permanent teeth Thin hair, poor nail growth Greater fat mass, decreased muscle mass and delayed bone formation Delayed puberty |
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ADH vasopressin
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is secreted by the posterior pituitary gland in response to changes in blood osmolality
ADH acts directly on the renal collecting ducts and distal tubules, increasing membrane permeability to and reabsorption of water |
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Antidiuretic Hormone Disorders
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Diabetes insipidus
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) |
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Diabetes Insipidus
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a disorder in which there is a large volume of urine that is hypotonic and dilute resulting from the inability to concentrate urine and conserve water as a result of the lack of vasopressin action (polyuria)
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Four pathophysiologic mechanisms related to vasopressin result from the following conditions
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Hypothalamic diabetes insipidus, with inability to secrete and usually to synthesize vasopressin in the neurohypophyseal system
Nephrogenic diabetes insipidus, inwhich there is an inapproriate renal response to vasopressin Transient diabetes insipidus of pregnancy, produced by the accelerated metabolism of vasopressin Primary poludipsia in which the initial pathophysiology involves the ingestion of fluid rather than the excretion of fluid |
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Dia Insip Etiology
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damage to the posterior pituitary, head trauma, intracranial tumors, neurosurgery, drugs, pregnancy, or idiopathic
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Diabetes Insipidus clinical manifestations
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large volume of dilute urine, thirst, increased serum sodium, neurological symptoms, dehydration, nocturia in adults and bedwetting in children
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SIADH
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produced when plasma levels of vasopressin are elevated at times during which the physiologic secretion of vasopressin from the posterior pituitary would normally be suppressed. Because the clinical abnormality is a decrease in the oxmotic pressure of body fluids, the hallmark of SIADH is hypo-osmolality
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SIADH simplified
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excretion of ADH and excessive water retention
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SIADH clinical manifestations
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hyponatremia, lethargy, confusion, cerevral edema, seizures, coma, muscle cramps, weakness, decreased urine output, fluid retention, wt. gain
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Thyroid Disease
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Thyroid hormone (T3 and T4) are produced in the thyroid gland.
Stimulated by TSH from pituitary Thyroid hormone stimulates growth and cellular metabolism T3 and T4 collectively are known as thyroid hormone |
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TH stimulates
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body growth, increases metabolic rate, heart rate, and glucose
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Iodine is
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necessary for the thyroid gland to synthesize and secrete hormones
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FSH secreted by the anterior pituitary
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stimulates the thyroid hormones!
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Thyroid hormone actions
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increased oxygen use
increased BMR increased heart production increased cardiac output increased ventilation gluconeogenesis enhanced SNS actions |
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Hyperthyroidism is more common in
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females (8x)
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Thyroid follicular cell hyperfunction with increased synthesis and secretion of T3 and T4
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Graves Disease
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Etiology of Hyperthyroidism
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Graves disease
Thyroid tumor Thyroiditis Pituitary adenoma Exogenous thyroid |
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Hyperthyroidism Clinical Manifestation
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weight loss
increased apetite nervousness heat intolerance palpitations increase bowel motility Warm, moist skin Thin hair Increased BP and HR Hyperrelexia Fine tremor Eyelid retraction, lag Enlarged thyroid |
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Graves disease pathophysiology
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IgG autoantibodies bind to and stimulate TSH receptors on thyroid. The result is excess production of TH which leads to a hypermetabolic state. Thyroid hyperplasia and hypersecretion result. Exophthalmos due to IgG (eyes)
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Pathophysiology of a goiter
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Enlargement of the thyroid gland in an attempt to compensate for inadequate TH
Maybe present in hyperthyroidism or hypothyroidism May be so large that it causes respiratory complications (benign or malignant) |
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Pathophysiology of Thyroid Storm
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Form of Life threatening thyrotoxosis that occurs when excessive amount of thyroid hormones are acutely released into circulation
Extreme state of hyperthyroidism Clinical manifestations are hyperthermia, tachycardia, agitation, seizures, exophthalmos, palpitations, restlessness, N&V&D |
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Thyroid hypofunction disorders
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Hypothyroidism
Myxedema / coma Iodine deficiency |
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Cretinism
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congenital hypothyroidsim due to thyroid dysgenesis
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Hypothyroidism
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Hashimoto thyroiditis (after they rupture, they are destroyed)
Iatrogenic (surgery, RAIU ablation) Iodine deficiency Pituitary failure Develops slowly |
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Hypothyroidism clinical manifestations in Infants
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Dull appearance, thick, protuberant tongue, and thick lips result in feeding difficulties
Prolonged neonatal jaundice Poor muscle tome Bradycardia, mottled extremities Umbilical hernia Hoarse cry |
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Hypothyroidism clinical manifestations in children/adults
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Decreased basal metabolic rate
Weakness, lethargy, cold intolerance, decreased appetite Bradycardia, narrowed pulse pressure, and mild/moderate weight gain Elevated serum cholesterol and tryglycerides Enlarged thyroid, dry skin, constipation Depression, difficulties with concentration.memory Menstrual irregularity Periorbital edema |
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Myxedema
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Generalized hypometabolic state occurring with untreated hypothyroidism
Accumulation of proteins in the interstitial spaces results in an increase in interstitial fluids causing edema Myxedema occurs in severe or prolonged hypothyroidism Altered metal state, altered thermoregulation, history of precipitating event Non-pitting edema is most commonly found in the pretibial and facial areas May progress to Myxedema coma!! |
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Iodine deficiency
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occurs as a result of antithyroid drugs, decreased iodine intake, or lithium
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Parathyroidism
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Detect serum calcium concentration and help maintain constant levels through the regulation of calcium absorption and resorption from bone
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Absorption of calcium
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is Vitamin D dependent and may be impaired in conditions in which VD is deficient (renal failure)
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Decrease in calcium =
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increase in PTH
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Hyperparathyroidism
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3:2 female, 50-60 years
PTH causes increased resorption of calcium, increased release of phosphorus and calcium by bones, icnreased bicarbonate excretion and decreased acid excretion leading to hypokalemia (low potassium) and metabolic acidosis |
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Hyperparathyroidism
Clinical manifestations |
depression, paresthesias, impaired vision, hypertension, nausea, abdominal pain, renal calculi, bone pain, bone demineralization, dehydration, may be asymptomatic
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85% of renal calculi are due to
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hyperparathyroidism
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Hypoparathyroidism
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very uncommon, usually due to removal of parathyroid gland during thyroidectomy, idiopathic, autoimmune
decrease in PTH which is inadequate to maintain normal serum calcium concentrations |
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Hypoparathyroidism Clinical manifestations
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dysrhythmias. abdominal cramps, irritability, anxiety, paresthesias, muscle spasms, dry scaly skin, tetany (spontaneous muscular contractions), carpal spasms, and laryngeal stridor.
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Adrenocortical Disorders
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Located superior to each kidney
Composed of medulla and cortex Medulla secretes catecholamines Cortex secretes mineral corticoids, glucocorticoids, androgens and estrogen |
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The function of ACTH
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is growth and development
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Function of aldosterone
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sodium retention and potassium excretion
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Function of glucocorticoids
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assisting body response to stress, increase serum glucose, suppress inflammation regulate metabolism of fats, carbs, proteins
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Adrenal cortical Hormones
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Sugar: glucocorticoids (cortisol)
Salt: mineralocorticoids (aldosterone) Sex: androgens and estrogens |
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Actions of Cortisol
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1. Metabolism: gluconeogenesis, insulin anagonist, increased appetite, mobilization of fat stores
2. Muscle: icnreased contractility, breakdown of protein to form glucose 3. Bone and Connective: decreased bone and collagen formation 4. Vascular: enhances effect of catecholamines, reduces vascular permeability, mineralocorticoid effects 5. Immune: inhibits the immune system in a number of ways 6. CNS: alters auditory, olfactory and tast acuity, mood, sleep |
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Cortisol diseases simplified
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Cushings: too much
Adisons: too little |
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Cortisol peak and nadir
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Peak: 2-4am
Nadir: 10-12midnight |
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Addision's disease
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hyposecretion of ACTH from the anterior pituitary or lack of CRH from from the hypothalamus
Generally occurs because of either destruction or dysfunction of the adrenal cortex or deficient pituitary ACTH Destruction of the adrenal gland through idiopathic or autoimmune mechanisms, tuberculosis, trauma or hemorrhage, fungal disease, or neoplasia |
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Addison's Disease Etiology
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autoimmune
adrenalectomy infaction congenital aplasia congenital enzyme deficiency sudden stress trauma pituitary failure steroid withdrawal |
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Addison's Disease Pathophysiology
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Destruction of adrenal cortical tissue leads to hypofunction of adrenal glands
Insufficient hormonal secretion of mineral corticoids and glucocorticoids reults in deficient aldosterone, cortisol and androgens Decreased aldosterone leads to increased sodium excretion, leading to hypotension and hyperkalemia |
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Addison's Disease Clinical Manifestations
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depression
hypotension EKG changes Muscle weakness Fatigue Skin hyperpigmentation Diarrea Nausea Anorexia Decreased libido Hyperkelemia** Hyponatremia** Hypoglycemia** |
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Cushings Syndrome (Hypercortisolism)
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adrenal cortex hyperfunction which results in excess production of cortisol and aldosterone
Clinical condition resulting from chronic exposure to excessive circulating levels of glucocorticoids Very common (more so in women) |
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Cushing Syndrome Etiology
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Disease: Pituitary adenoma
Syndrome: Adrenal adenoma, adrenal carcinoma, Ectopic ACTH (cancer), exogenous steroids |
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Cushing Syndrome Clinical Manifestations
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Weight gain
Fatigue Menstural irregularity Weakness Easy bruising Peptic ulcers Poor wound healing Decreased libido Hyperkalemia Central Obesity Muscle wasting Striae Hyperglycemia Hypertension Hirsutism (Moonface) ** Buffalo hump** Acne Glycosuria |
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Renin-Angiotensin
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Renin into blood
Renin converted to angiotensin I Angiotensin I converted to angiotensin II in lungs Angiotensin II stimulates secretion of Aldosterone |
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Hyperaldosteronism
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Excessive production of aldosterone by the adrenal cortex thought to be the most common potentially curable treatable cause of hypertension
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Hyperaldosteronism
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Rare, caused by adrenal tumor or excessive circulating renin
Pathophysiology--increased aldosterone secretion Clinical manifestations are hpertension, hypokalemia, renal damage, cerebral infarcts, fluid retention, tetany, electrolyte imbalance, muscle weakness |
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Adrenal Medullary Disorders:
Pheochromocytoma |
catecholamine-secreting tumor of the adrenal medulla. (norepinephrine and epinephrine)
Incidence--rare, causes severe hypertension Etiology-- neoplasia syndromes Pathogenesis-- tumor causes excressive secretion of epinephrine and norepinephrine Clinical manifestations are hypertension, agitation, headaches, palpitations, tachycardia, N&V, diarrhea, polyuria, tremors |
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Addison's Disease Etiology
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autoimmune
adrenalectomy infaction congenital aplasia congenital enzyme deficiency sudden stress trauma pituitary failure steroid withdrawal |
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Addison's Disease Pathophysiology
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Destruction of adrenal cortical tissue leads to hypofunction of adrenal glands
Insufficient hormonal secretion of mineral corticoids and glucocorticoids reults in deficient aldosterone, cortisol and androgens Decreased aldosterone leads to increased sodium excretion, leading to hypotension and hyperkalemia |
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Addison's Disease Clinical Manifestations
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depression
hypotension EKG changes Muscle weakness Fatigue Skin hyperpigmentation Diarrea Nausea Anorexia Decreased libido Hyperkelemia** Hyponatremia** Hypoglycemia** |
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Cushings Syndrome (Hypercortisolism)
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adrenal cortex hyperfunction which results in excess production of cortisol and aldosterone
Clinical condition resulting from chronic exposure to excessive circulating levels of glucocorticoids Very common (more so in women) |
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Cushing Syndrome Etiology
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Disease: Pituitary adenoma
Syndrome: Adrenal adenoma, adrenal carcinoma, Ectopic ACTH (cancer), exogenous steroids |
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Cushing Syndrome Clinical Manifestations
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Weight gain
Fatigue Menstural irregularity Weakness Easy bruising Peptic ulcers Poor wound healing Decreased libido Hyperkalemia Central Obesity Muscle wasting Striae Hyperglycemia Hypertension Hirsutism (Moonface) ** Buffalo hump** Acne Glycosuria |
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Renin-Angiotensin
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Renin into blood
Renin converted to angiotensin I Angiotensin I converted to angiotensin II in lungs Angiotensin II stimulates secretion of Aldosterone |
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Hyperaldosteronism
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Excessive production of aldosterone by the adrenal cortex thought to be the most common potentially curable treatable cause of hypertension
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Hyperaldosteronism
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Rare, caused by adrenal tumor or excessive circulating renin
Pathophysiology--increased aldosterone secretion Clinical manifestations are hpertension, hypokalemia, renal damage, cerebral infarcts, fluid retention, tetany, electrolyte imbalance, muscle weakness |
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Adrenal Medullary Disorders:
Pheochromocytoma |
catecholamine-secreting tumor of the adrenal medulla. (norepinephrine and epinephrine)
Incidence--rare, causes severe hypertension Etiology-- neoplasia syndromes Pathogenesis-- tumor causes excressive secretion of epinephrine and norepinephrine Clinical manifestations are hypertension, agitation, headaches, palpitations, tachycardia, N&V, diarrhea, polyuria, tremors |
