NURS 241 Exam 3 Factors Affecting Response of a Target Cell to a

Endocrine Disorders Hormone:

– Number of receptors present
Endocrine Systems: • Up regulation
– Intercellular communication network • Down regulation
– Hormones travel from cell to cell through the – Affinity of these receptors for hormones
bloodstream. • Affected by a number of conditions
– Regulates complex phenomena • Example: the pH of the body fluids plays an
• Stress response important role in the affinity of insulin receptors
• Growth and development Control of Hormone Levels:
• Fluid and electrolyte balance – Affected by diurnal fluctuations that vary with
• Reproduction the sleep–wake cycle
Functions of the Endocrine System: • Growth hormone (GH) and
– Growth and development adrenocorticotropic hormone (ACTH)
– Sex differentiation – Secreted in a complicated cyclic manner
– Metabolism • Female sex hormones
– Adaptation to an ever changing environment – Regulated by feedback mechanisms that
• Regulation of digestion monitor substances such as glucose (insulin) and
• Use and storage of nutrients water (ADH) in the body
• Electrolyte and water metabolism – Regulated by feedback mechanisms that involve
• Reproductive functions the hypothalamic pituitary target cell system
Hormones:
– Function as chemical messengers Negative Feedback:
• Move through the blood to distant target – Feedback signals decrease secretion by
sites of action • Down regulation of receptor number
• Can also act more locally as paracrine or • Decreased sensitivity of receptors
autocrine messengers that incite more local • For example, thyroid hormone down regulates
effects TRH receptors on thyrotroph cells in the
• Most are present in body fluids at all times pituitary
in greater or lesser amounts as needed Feedback Loops:
– Characteristics – Ultra short loop
• A single hormone can exert various effects • Within the hypothalamus
in different tissues – Short loop
• A single function can be regulated by • From pituitary to hypothalamus
several hormones – Long loop
• From target organ to hypothalamus &
Categories of Hormones According to Structure: pituitary
– Amines and amino acids
– Peptides, polypeptides, proteins & glycoproteins Categories or Disturbances of Endocrine
– Steroids Function:
– Fatty avid derivative – Hypofunction: underproduction of hormone
• Causes:
Solubility of Hormones Determines Mechanism of - Congenital defects
Actions: - Disruption in blood flow, infection,
– Lipid soluble hormones inflammation, autoimmune responses, or
• Steroid neoplastic growth
• Thyroid - Decline in function with aging
– Water soluble hormones - Atrophy as the result of drug therapy or
• Proteins and peptides unknown reasons
• Catecholamines - Receptor defects
• Etiology:
- Autoimmune inhibition
 - Nonsecreting tumors – Usually occur gradually
- Surgical removal – Can present as an acute and life threatening
- Ischemia, infarct condition
- Receptor defects – Symptoms:
• Treatment: • Being chronically unfit
- Hormone therapy • Weakness and fatigue
• Loss of appetite
– Hyperfunction: excessive hormone production • Impairment of sexual function
• Causes: • Cold intolerance
- Excessive stimulation and hyperplasia of
the endocrine gland Measurement of Hypothalamin Pituitary Target
- Hormone producing tumor of the gland Cell Hormones:
• Etiology: – Serum cortisol
- Autoimmune stimulation – Serum prolactin
- Secreting tumors – Serum thyroxine and TSH
- Idiopathic – Serum testosterone (male)/serum estrogen
• Treatment: (female) and serum LH/FSH
- Surgical removal – Serum GH/insulin like growth factor 1
- Blocking drugs – Plasma osmolality and urine Osmolality
- Irradiation
Hormones Essential for Normal Body Growth &
Categories of Endocrine Disorders: Maturation
– Primary Disorders: – Growth hormone (GH)
• Originate in the target gland responsible for – Insulin
producing the hormone – Thyroid hormone
– Secondary Disorders: – Androgens
• The target gland is essentially normal, but its
function is altered by defective levels of Growth Hormone:
stimulating hormones or releasing factors – Produced by somatotropes in the anterior
from the pituitary system pituitary
– Tertiary Disorders: – Necessary for linear bone growth in children
• Result from hypothalamic dysfunction – Stimulates cells to increases in size and divide
• Both the pituitary and target organ are more rapidly
understimulated – Enhances amino acid transport across cell
membranes
Primary vs. Secondary Disorders: – Decreases the rate at which cells use
– Primary disorders are due to dysfunction of the carbohydrates
target gland
– Secondary disorders are due to dysfunction of Growth Hormone in Children
the pituitary gland – GH deficiency:
– Primary and secondary disorders can be • Interferes with linear bone growth
differentiated by looking at feedback loops • Results in short stature or dwarfism
– GH excess:
Categories of Pituitary Tumors: • Results in increased linear bone growth
– Primary tumors • Gigantism
– Secondary tumors
• Metastatic lesions Effects of Growth Hormone Excess in Adults:
– Functional tumors – Overgrowth of the cartilaginous parts of the
• Secrete pituitary hormones skeleton
– Nonfunctional tumors – Enlargement of the heart and other organs of the
• Do not secrete hormones body
Manifestations of Hypopituitarism: – Metabolic disturbances resulting in altered fat
 metabolism and impaired glucose tolerance Altered GH Secretion:
– Too much GH
Causes of Short Stature: • Children tall stature
– Variants of normal • Adults acromegaly
– Low birth weight – Too little GH
– Chronic illness and malnutrition • Children short stature
– Functional endocrine disorders • Adult decreased muscle?
– Chromosomal disorders Evaluation of Short Stature:
– Skeletal abnormalities – Routine assessment of height and weight
– Unusual syndromes • Plot on growth curve
– Genetic short stature: • Watch for “falling off the curve”
• Well proportioned and have a height close to • Often occurs in later childhood or puberty
the midparental height of their parents – Assess parental height
– Constitutional short stature: – Inquire about parental and sibling growth
• Moderately short stature, thin build, delayed pattern—delayed puberty?
skeletal and sexual Differential Diagnosis of Short Stature:
maturation, and absence of other causes – Constitutional (normal)
of decreased growth – Delayed puberty
– Protein calorie malnutrition – Pituitary failure (1:4000 children)
– Chronic diseases • Isolated GH deficiency
• End stage renal disease • Multiple anterior pituitary hormones
• Poorly controlled diabetes mellitus – Other
– Malabsorption syndromes • Chronic disease, Turner syndrome,
– Excessive glucocorticoid administration malnutrition, bone disease, etc.
– Emotional disturbances Diagnostic Testing:
– Evaluation of bone age
Tall Stature: • Refer for radiologic exam of epiphyseal
– Constitutional tall stature plate
• A child who is taller than his or her peers – Growth hormone assay
and is growing at a velocity that is within – Growth hormone provocation tests
the normal range for bone age • Arginine, hypoglycemia
– Genetically tall Acromegaly:
– Other causes – When GH excess occurs in adulthood or after
• Marfan syndrome: genetic condition that epiphysis of long bones have fused GH secreting
results in rapid bone growth and pituitary adenoma
late/absence of epiphyseal capping • Headache, visual disturbances
• Endocrine causes • Hyperglycemia “diabetogenic”
 Sexual precocity: early onset of • Increased lean body mass
estrogen and androgen secretion  Bone and soft tissue
and excessive GH – Treatment:
• Hypophysectomy
Growth Hormone: • Irradiation
– Secreted from anterior pituitary somatotrophs in – Treatment Goals:
response to increased GHRH and decreased • Normalization of the GH response to an oral
somatostatin glucose load
– GH is secreted in pulses with most secretion • Normalization of IGF 1 levels to age and
during sleep sex matched control levels
– 191 amino acid peptide with a circulatory T1/2 of • Removal or reduction of the tumor mass
20 min • Relieving the central pressure effects
– Somatomedins have T1/2 of 20 hr • Improvement of adverse clinical features
• Normalization of the mortality rate

Causes of Acromegaly:
– Most common cause (95%)
• Somatotrope adenoma
– Other causes (<5%)
• Excess secretion of GHRH by hypothalamic
tumors
• Ectopic GHRH secretion by non endocrine
tumors such as carcinoid tumors or small
cell lung cancers
• Ectopic secretion of GH by non endocrine
tumors
Precocious Puberty:
– Isosexual precocious puberty is early activation
of the hypothalamic pituitary gonadal axis
– Results in development of appropriate sexual
characteristics and fertility
– Persons with precocious puberty usually are tall
for their age as children but short as adults
because of the early closure of the epiphyses
Causes of Precocious Sexual Development:
– Idiopathic
– Gonadal disease
– Adrenal disease
– Hypothalamic disease
– Benign and malignant tumors of the central
nervous system
Major Functions of Thyroid Hormone:
– Increases metabolism and protein synthesis
– Influences growth and development in children
• Mental development and attainment of
sexual maturity
Three Major Thyroid Binging Proteins:
– Thyroid hormone–binding globulin (TBG)
• Carries approximately 70% of T4 and T3
– Thyroxine binding prealbumin (TBPA)
• Binds approximately 10% of circulating T4 and
lesser amounts of T3
– Albumin
• Binds approximately 15% of circulating T4 & T3
Alterations of Thyroid Function:
– Hypothyroidism
• Decreased metabolic rate
• Accumulation of hydrophilic
mucopolysaccharide substance (myxedema) in
the connective tissues
• Elevated serum cholesterol
– Hyperthyroidism
• Increased metabolic rate and oxygen
consumption
• Increased use of metabolic fuels
• Increased sympathetic nervous system
responsiveness
Manifestations of Hypothyroidism:
– Mental and physical sluggishness
– Somnolence
– Decreased cardiac output, bradycardia
– Constipation
– Decreased appetite
– Hypoventilation
– Cold intolerance
– Coarse dry skin and hair
– Weight gain
Manifestations of Hyperthyroidism:
– Restlessness, irritability, anxiety
– Wakefulness
– Increased cardiac output
– Tachycardia and palpitations
– Diarrhea, increased appetite
– Dyspnea
– Heat intolerance, increased sweating
– Thin and silky skin and hair
– Weight loss
Hyperthyroidism:
– HISTORY:
• Weight loss, increased appetite, nervousness,
heat intolerance, palpitations, increased bowel
motility
– PHYSICAL:
• Warm, moist skin, thin, fine hair, increased BP,
HR, hyperreflexia, fine tremor, eyelid retraction,
lag, enlarged thyroid
Hypothyroidism:
– HISTORY
• Weight gain, fatigue, amenorrhea, cold
Tolerance, constipation
– PHYSICAL:
• Dry, dull skin, coarse hair, hoarse voice, low
HR, BP, decreased DTR, periorbital edema
Measures Used to Diagnose Thyroid Disorders
–Measures of T3, T4, and TSH
– Resin uptake test
– Assessment of thyroid autoantibodies
– Radioiodine (123I) uptake test
– Thyroid scans (i.e., 123I, 99mTc pertechnetate)
– Ultrasonography
 – CT and MRI scans • Serve mainly as source of androgens for
– Fine needle aspiration (FNA) biopsy of a thyroid women
nodule
Actions of Cortisol:
Graves Disease: – Glucose metabolism
– State of hyperthyroidism, goiter and – Protein metabolism
ophthalmopathy (less commonly, dermopathy) – Fat metabolism
– An autoimmune disorder characterized by abnormal – Anti inflammatory action
stimulation of the thyroid gland by thyroid – Psychic effect
stimulating antibodies (thyroid stimulating – Permissive effect
immunoglobulins [TSI]) that act through the normal
TSH receptors Clinical Findings of Adrenal Insufficiency:
– Is associated with human leukocyte antigen (HLA) – Anorexia and weight loss
DR3 and HLA B8 – Fatigue and weakness
– Familial tendency is evident – Gastrointestinal symptoms, nausea, diarrhea
– Myalgia, arthralgia, abdominal pain
Pathophysiology: – Orthostatic hypotension
– Etiology: autoimmune – Hyponatremia
• High association with HLA D3 and B8 – Hyperkalemia
• Women affected more often than men 8:1 – Hyper pigmentation
– Pathogenesis – Secondary deficiency of select hormones
• IgG autoantibodies bind to and stimulate TSH – Associated autoimmune conditions
receptors on thyroid.
• Thyroid hyperplasia and hypersecretion result. Stages of Adrenal Cortical Insufficiency:
– Exophthalmos due to IgG – Primary adrenal cortical insufficiency (Addison’s
disease)
Treatment: – ACTH levels are elevated because of lack of
– RAIU ablation feedback inhibition
– Symptom control with β blockers – Secondary adrenal cortical insufficiency
– PTU and thyroxine to inhibit synthesis • Occurs as a result of hypopituitarism or because
• Thyroxine may reduce relapse, which often pituitary gland has been surgically removed
occurs with PTU alone. – Acute adrenal crisis
– Surgery - ***Life threatening situation occurs***

Manifestations of Thyroid Storm: Glucocorticoid Hormone Excess:

– Very high fever – Cushing syndrome (hypercortisolism) know
– Extreme cardiovascular effects symptoms
• Tachycardia, congestive failure, and angina • Pituitary form results from excessive production
– Severe CNS effects of ACTH by a tumor of the pituitary gland
• Agitation, restlessness, and delirium • Adrenal form caused by a benign or malignant
– **High mortality rate** adrenal tumor
• Ectopic form, nonpituitary ACTH secreting
Steroid Hormones Produced by the Adrenal Cortex: tumor
– Mineralcorticoids (aldosterone) • Altered fat metabolism
• Function in sodium, potassium, and water • Muscle weakness
balance • Muscle wasting
– Glucocorticoids (cortisol) • Purple striae
• Aid in regulating the metabolic functions of the • Osteoporosis
body and in controlling inflammatory response • Derangements in glucose metabolism
• Essential for survival in stress situations • Hypokalemia
– Adrenal sex hormones (androgens) • Gastric acid secretion
• Hirsutism, mild acne, & menstrual irregularities

Congenital Adrenal Hyperplasia:
– Genetic
– Common Enzyme Deficiencies associated cortisol
production
• 21 hydroxylase (accounting for >90% of cases)
• 11 β hydroxylase deficiency
EXAM QUESTIONS:
– Thyroid storm results in delayed puberty.. FALSE
results in high temperatures
– A ______ disorder results from lesions or damage
at the target gland..PRIMARY
– Which of the following is a cause of tall stature?
MARFAN SYNDROME
Neoplasia
– Neoplasia new abnormal development of cells that
may be benign or malignant
– Neoplasm abnormal growth of tissue may be
benign or malignant (tumor)
– Cancer in situ neoplastic changes localized to
tissue of origin (preinvasive)
Cancer:
– 2nd leading cause of death in the US
– 1.45 million new cases in 2007 in the US
– Aprox 62% of new cancer cases are alive 5 years
later
– Survival depends on type of cancer and extent of
disease at diagnosis
– Affects all age groups
– Can originate in almost any organ
– Cancer By New Cases:
• Men  prostate  lung  colon
• Women  breast  lung  colon
– Cancer By Death:
• Men  lung  prostate  colon
• Women  lung  breast  colon
• –
Characteristics of Cancer:
– Disorder of altered cell differentiation and growth
• Results in neoplasia (“new growth”)
– Growth is uncoordinated and relatively autonomous
• Lacks normal regulatory controls over cell
growth and division
• Tends to increase in size and grow after
stimulus ceases or needs of
organism are met
Mechanisms of Cancer:
– Cancers are now thought to derive from tissue stem
cells that are capable of proliferation
– 80% to 90% of cancers are epithelial in origin.
– Cancer is attributed to mutations that enhance
proliferation.
– These mutations allow the stem cell clone to ignore
normal environmental signals
What Happens to growth control on cancer?
– Uncontrolled cell replication
– Cell immortality
– Anchorage independence
– Accumulation of mutations that allow malignant
behavior of the clone over time
Components of Tissue Renewal and Repair
– Cell proliferation
• Process of cell division
• Inherent adaptive mechanism for replacing body
cells
– Cell differentiation
• Process of specialization
• New cells acquire the structure and function of
cells they replace
– Apoptosis
• Form of programmed cell death to eliminate
unwanted cells
– The Cell Cycle:
– The interval between each cell division
– General information is duplicated
• Duplicated chromosomes are appropriately
aligned for distribution between two genetically
identical daughter cells
– Checkpoints in cycle provide opportunities for
monitoring the accuracy of deoxyribonucleic acid
(DNA) replication
• Edited and repaired defects ensure full
complement of genetic
information to each daughter cell
– Phase of the Cell Cycle: maybe
G1 (gap 1): the post mitotic phase
• DNA synthesis ceases while ribonucleic acid
(RNA) and protein synthesis and cell growth
take place
– S phase: DNA synthesis occurs, giving rise to two
separate sets of chromosomes, one for each
daughter cell
– G2 (gap 2): the premitotic phase
• DNA synthesis ceases; RNA and protein
synthesis continues
– M phase: the phase of cellular division or mitosis
Cell Proliferation:
– The process by which cells divide and reproduce
– Regulation:
• Regulated in normal tissue, so the number of
cells actively dividing equal the number of cells
dying or being shed
Categories of Cell Types of the Body:
– Well differentiated neurons and cells of skeletal and
cardiac muscle unable to divide and reproduce
– Parent or progenitor cells that continue to divide
and reproduce
• Blood cells, skin cells, liver cells
– Undifferentiated stem cells that can be triggered to
enter cell cycle and produce large numbers of
progenitor cells when needed
Stem Cells:
– Definition: reserve cells that remain quiescent until
there is a need for cell replenishment
– When a stem cell divides, one daughter cell retains
the stem cell characteristics, and the other daughter
cell becomes a progenitor cell that proceeds
through to terminal differentiation
– Self renewal
– Potency
Types of Stem Cells: maybe
Unipotent: give rise to one type of
differentiated cell
Muscle satellite cell
Epidermal stem cell
Spermatogonium
Basal cell of the olfactory epithelium
Olgipotent: produce small number of cells
Pluripotent: give rise to numerous cell types
Tumors:
Mass of cells due to overgrowth
Neoplasms
Malignant
Benign
Named by adding the suffix oma to the
parenchymal tissue type from which the growth
originated
Types of Tumors:
Adenoma: benign tumor of glandular epithelial
tissue
Adenocarcinoma: malignant tumor of glandular
epithelial tissue
Carcinoma: malignant tumor of epithelial tissue
Osteoma: benign tumor of bone tissue
Sarcoma: malignant tumors of mesenchymal
origin
Papillomas: benign microscopic or macroscopic
fingerlike projections growing on a surface
Factors Differentiating Benign and Malignant
Neoplasms:
Cell characteristics
Manner of growth
Rate of growth
Potential for metastasizing or spreading
Ability to produce generalized effects
Tendency to cause tissue destruction
Capacity to cause death
Characteristics of Benign Neoplasms:
A slow, progressive rate of growth that may
come to a standstill or regress
An expansive manner of growth
Inability to metastasize to distant sites
Composed of well differentiated cells that
resemble the cells of the tissue of origin
Characteristics of Malignant Neoplasms:
Tend to grow rapidly and spread widely
Have the potential to kill regardless of their
original location
Tend to compress blood vessels and outgrow
their blood supply, causing ischemia and tissue
necrosis
Rob normal tissues of essential nutrients
Liberate enzymes and toxins that destroy tumor
tissue and normal tissue
Metastasis:
Spread of a malignant tumor to a distant site
Methods by Which Cancer Spreads:
Direct invasion and extension
Seeding of cancer cells in body cavities
Metastatic spread through the blood or lymph
pathways
Factors Affecting Tumor Growth:
The number of cells that are actively dividing
or moving through the cell cycle
The duration of the cell cycle
The number of cells that are being lost
compared with the number of new cells being
produced
Steps Involving the Transformation of Normal Cells
into Cancer Cells:
Initiation
Cells exposed to doses of carcinogenic
agents making them susceptible to malignant
transformation
 Promotion: Carcinogens
Unregulated accelerated growth in Food fried in reused fat
already initiated cells caused by various chemicals and Alcohol
growth factors Nitrites
Progression: Plastic and chemicals
Tumor cells acquire malignant Lack of antioxidants
phenotypic changes that promote Clinical Manifestations of Cancer:
invasiveness, metastatic competence, Cancer Cachexia
autonomous growth tendencies, and increased Weight loss and wasting of body fat and
karyotypic instability muscle tissue; profound weakness,
Host & Environmental Factors Leading to Cancer: anorexia, and anemia
Obesity Paraneoplastic Syndromes
Heredity Manifestations in sites not directly
Hormones affected by the disease
Carcinogens Tissue Integrity
Chemical Compressed and eroded blood vessels,
Radiation ulceration and necrosis, frank
Oncogenic viruses bleeding, and hemorrhage
Immunologic mechanisms Diagnostic Measures for Cancer Detection:
Pap smear
Genes that Control Cell Growth & Replication: Biopsy
Proto oncogenes Tumor markers
Tumor suppressor genes Antigens on surface of tumor or
Genes that control programmed cell death or Released from normal cells in response
apoptosis to the presence of a tumor
Genes that regulate repair of damaged DNA Present in benign conditions
Genetic Bases of Cancer: Not elevated in early stages of
Cancer is caused by genetic mutations malignancy
Two important classes of genes are involved CA 125 & PSA
Overactivity of proto oncogenes Staging and grading of tumors
Inactivation of tumor suppression genes (anti Goals of Cancer Treatment:
oncogenes) Curative, control, palliative
Proto Oncogenes Code For: How Do Benign & Malignant Tumors Differ?
Growth factors Benign: OMA
Growth factor receptors Strictly local, no metastasis, well
Intracellular pathway components differentiated
Transcription factors Malignant: SARCOMA
Overactivation  proliferation Invasive, metastatic potential, rapidly
Tumors Suppression Genes Inhibit Cell Replication: growing, anaplastic
pRB: master brake of the cell cycle, inhibits Staging & Grading of Tumors:
transcription Staging: according to clinical spread
TP53: suicide gene, causes apoptosis of errant description of location and spread of
cells tumors in the body
Chemical Carcinogens: T: tumor (size, local, or invasive)
Thousands of natural and man made substances N: nodes (no, yes, distant)
are mutogenic. M: metastasis (no, yes)
Exposure through inhalation, topical contact, or Grading: according to histologic or cellular
ingestion characteristics
Asbestos mesothelioma Histologic analysis of degree of
Vinyl chloride liver cancer anaplasia
Napthylamine bladder cancer Cancer Treatment Modalities:
Host & Environmental Factors Leading to Cancer: Surgery, radiation, hormonal therapy, targeted
therapy Osteosarcoma
Biotherapy Ewing’s sarcoma
Immunotherapy: changing the person’s Characteristics of Childhood Cancer:
own immune response to cancer Most involve the hematopoietic system,
Biologic response nervous system, or connective tissue
Chemotherapy Heritable forms of cancer tend to have:
Direct DNA interacting An earlier age of onset
Indirect DNA interacting A higher frequency of multifocal lesions
Cell cycle specific in a single organ
Cell cycle noonspecific Bilateral involvement of paired organs
What Side Effects Are Likey to Occur in Persons or multiple primary tumors
Receiving Radiation or Chemo? Obstruction:
Bone marrow depression: anemia, Blockage of any hollow tubular structure that
thrombocytopenia, leukopenia prevents normal passage
Mucosal sloughing and alopecia Airways, blood vessels, GI tract, biliary ducts,
Pain, nausea Eustachian tube, brain/CSF, urethra/ureters, lymph
Stem Cell Transplantation: vessels, sinuses, glands
Bone marrow transplantation (BMT) Signs of Outflow Obstruction & Urine Retention:
Peripheral blood stem cell transplantation Bladder distention
(PBSCT) Hesitancy
Two treatment approaches for Straining when initiating urination
individuals with leukemias, certain solid Small and weak stream
tumors, and other cancers previously thought to Frequency
be incurable Feeling of incomplete bladder emptying
Types of Surgery for Cancer: Overflow incontinence
Cryosurgery: instilling liquid nitrogen into the Causes of Pancreatic Cancer:
tumor through a probe The cause of pancreatic cancer is unknown
Chemosurgery: using corrosive paste with Smoking appears to be a major risk factor
multiple frozen sections to ensure complete The second most important factor appears to be
removal of tumor diet
Laser surgery: using a laser beam to resect Increasing total calorie intake
tumor High intake of fat, meat, salt,
Laparoscopic surgery: performing surgery dehydrated foods, fried foods, refined sugars, soy
through two small incisions beans, and nitrosamines
Cancer Routinely Screened: Manifestations of Liver Failure:
Breast (clinical breast exam and mammogram) Hematologic disorders
Uterine (clinical palpation for size, Endocrine disorders
irregularities) Skin disorders
Cervical (speculum exam and Pap smear) Hepatorenal syndrome
Skin (visual inspection) Hepatic encephalopathy
Lymphomas (palpation of lymph nodes)
Prostate (digital rectal examination, PSA Acid Base Balance
testing)
Testicular (palpation) Acid Base Balance:
Leukemia (complete blood cell count) Metabolic activities require precise acid base
Colorectal (fecal occult blood, colonoscopy balance, which is reflected in the pH of extracellular
Common Solid Tumors of Childhood: fluids
Brain and nervous system tumors Acid: a molecule that can release hydrogen ion
Neuroblastoma (H+)
Wilms’ tumor Base: a molecule that can accept or combine
Rhabdomyosarcoma and embryonal sarcoma with a hydrogen ion (H+)
Retinoblastoma H2CO3: Carbonic Acid
 CO2: Carbon Dioxide
HCO3: Bicarbonate
Factors Dependent Upon Acid Base Balance
Regulation:
Narrow range of optimal function
Membrane excitability
Enzyme systems
Chemical reactions
Principles of Acid Base Balance:
The Body tightly regulates pH
Normal range: 7.35 7.45
pH Buffering:
H+ + HCO3  H2CO3  CO2 + H2O
Kidneys regulate bicarbonate
Lungs regulate carbon dioxide
One system can compensate for the other to
keep ratio near 20:1
Arterial Blood Gas Norms:
pH: 7.35 7.45
PaCO2: 35 45 mm Hg
HCO3–: 22 26 mEq/L
pH:
Normal pH = 7.4
pH < 6.8 or >7.8 can lead to cellular death
Mechanisms of Acid Base Balance:
pH of extracellular fluid must be maintained
within 7.35 to 7.45 for optimal functioning of body
cells
pH is determined by the ratio of the bicarbonate
base to the volatile carbonic acid (normally 20 to 1)
The concentration of metabolic acids and
bicarbonate base is regulated by the kidney
The concentration of CO2 is regulated by the
respiratory system
Extracellular and intracellular systems buffer
changes in pH that occur due to metabolic production
of volatile and nonvolatile acids
Processes Involved in the Regulation of Plasma
Concentration of HCO:
Reabsorption of the filtered bicarbonate
Generation of new bicarbonate
By excretion of nonvolatile acids
Lab Tests Used in Assessing Acid Base Balance:
Arterial blood gases and pH
CO2 content and HCO3– levels
Base excess or deficit
The anion gap
Assess for Anion Gap Acidosis
Low Gap <6
Multiple myeloma protein
High Gap >12
Ketoacidosis, lactic acidosis, salicylate
toxicity, methanol, ethylene, glycol
Normal Gap
Loss of HCO3
Respiratory Acidosis:
Cause: decreased alveolar ventilation
Signs and symptoms: CNS depression,
headache, cardiac dysrhythmias
Compensation: kidneys increase HCO3– (slow)
Respiratory Alkalosis:
Cause: increased alveolar ventilation
Signs and symptoms: CNS irritability,
lightheaded, cardiac dysrhythmias
Compensation: kidneys excrete more HCO3–
(slow)
Metabolic Acidosis
Cause: acid accumulation or loss of bicarbonate
Signs and symptoms: CNS depression,
headache, cardiac dysrhythmias
Compensation: lungs excrete more CO2 (fast)
Metabolic Alkalosis:
Cause: accumulation of bicarbonate or acid loss
Signs and symptoms: CNS irritability, cardiac
dysrhythmias
Compensation: lungs retain more CO2 (fast)
Metabolic Acidosis:
Primary disturbance
Decrease in bicarbonate
Respiratory Compensation
Hyperventilation to decrease PCO2
Renal Compensation
If no renal disease, increased H+
excretion and increased HCO3–
reabsorption
Causes of Metabolic Acidosis:
Excess metabolic acids
Excessive production of metabolic acids
Impaired elimination of metabolic acids
Excessive bicarbonate loss
Loss of intestinal secretions
Increased renal losses
Increased chloride levels
Manifestations of Metabolic Acidosis:
Increased extracellular H+ ion concentration
Decrease in pH (<7.35)
Decrease in HCO3– levels (<24 mEq/L)
Metabolic Alkalosis:
Primary disturbance
Increase in bicarbonate
Respiratory compensation
Hypoventilate to increase PCO2
 Renal compensation Hypoxia and reflex stimulation of
If no renal disease, decreased H+ ventilation
excretion and decreased HCO3– reabsorption Lung disease that reflexively stimulates
Causes of Metabolic Alkalosis: ventilation
Excessive gain of bicarbonate or alkali Stimulation of respiratory center
Excessive loss of hydrogen ions Mechanical ventilation
Increased bicarbonate retention Manifestations of Respiratory Alkalosis:
Volume contraction Decrease in PCO2
Manifestations of Metabolic Alkalosis: Deficit in H2CO3
Increase in pH due to a primary excess of The pH is above 7.45, arterial PCO2 is below
plasma HCO3– ions 35 mm Hg, and plasma HCO3– levels usually are below
Caused by: 24 mEq/L (24 mmol/L)
Loss of H+ ions Neural Function
Net gain in HCO3 Constriction of cerebral vessels and
Loss of Cl– ions in excess of HCO3– increased neuronal excitability
ions Cardiovascular function
Signs of Compensation: Cardiac dysrhythmias
Decreased rate and depth or respiration
Increased urine H Compensations:
Renal for respiratory imbalances
Respiratory Acidosis: Respiratory or metabolic imbalances
Primary disturbance
Increase in PCO2 Categories of the Manifestations on Acidosis:
Respiratory compensation S&S of he disorder causing acidosis
None Changes in body function related to recruitment
Renal compensation of compensatory mechanisms
Increased H+ excretion and increased Alterations in cardiovascular, neurologic, and
–
HCO3 reabsorption musculoskeletal function resulting from the
Causes of Respiratory Acidosis: decreased pH
Occurs in acute or chronic conditions that
impair effective alveolar ventilation and cause an Sources of the Body’s Plasma HCO3:
accumulation of PCO2 CO2 that is produced during metabolic
Impaired function of the respiratory processes
center in the medulla (as in narcotic Reabsorption of filtered HCO3–
overdose) Generation of new HCO3– by the kidney
Lung disease
Chest injury Respiratory Control of pH:
Weakness of the respiratory muscles Lungs retain or eliminate CO2
Airway obstruction CO2 retention decreases pH
CO2 elimination increases pH
Respiratory Alkalosis: Renal Control of pH:
Primary disturbance Kidneys retain or eliminate HCO3
Decrease in PCO2 HCO3 retention increases pH
Respiratory compensation HCO3 elimination decreases pH
None Potassium Hydrogen Ion Exchange:
Renal compensation Excess H+ in the ECF causes
Decreased H+ excretion and decreased H+ to move into cells
–
HCO3 reabsorption K+ to move out of cells into ECF
Causes of Respiratory Alkalosis:
Excessive Ventilation Ion Exchange:
Anxiety and psychogenic Acidosis:
hyperventilation High potassium calcium
 Alkalosis:
Low potassium and low calcium
General Therapy for Acid Base Disorders:
Respiratory acidosis
Measures to improve ventilation
Respiratory alkalosis
Find cause: anxiety, hypoxemia
Metabolic acidosis
Give NaHCO3 for bicarb deficiency
Correct underlying cause
Lactic acidosis
Ketoacidosis
Acute renal failure
Metabolic alkalosis
Find cause
Antacids?asprins?
K+, Cl– imbalance
Can give acid (HCl) but not
often done
Diabetes Mellitus
Diabetes Mellitus:
Multisystem disease
Disorder of glucose metabolism:
Abnormal insulin production or
impaired insulin utilization
About 1/3 of the people with diabetes are not
diagnosed and do not know they have it
Secondary Conditions Associated with Diabetes:
Risk factor in coronary heart disease and stroke
Leading cause of blindness
Leading cause of end stage renal disease
Major contributor to lower extremity
amputations
Glucose, Fats, Proteins:
Energy needs in the body
The liver, with hormones from the endocrine
pancreas, regulates energy production
Glucose is metabolized to CO2 and H2O.
Fat is metabolized to glycerol and fatty acids
Protein is metabolized to amino acids
Tissues Types and Functions of the Pancreas:
The acini
Secrete digestive juices into the
duodenum
The islets of Langerhans
Secrete hormones into the blood
Composed of beta cells that secrete
insulin, alpha cells that secrete
glucagon, and delta cells that secrete
somatostatin
Actions of Insulin & Glucogon:
Insulin: anabolic
Increases glucose transport into skeletal
muscle and adipose tissue
Increases glycogen synthesis
Decreases gluconeogenesis
Glucagon: catabolic
Promotes glycogen breakdown
Increases gluconeogenesis
Actions of Insulin on Glucose, Fats, and Proteins:
Anabolic in nature
Promotes glucose uptake by target cells and
provides for glucose storage as glycogen
Prevents fat and glycogen breakdown
Inhibits gluconeogenesis and increases protein
synthesis
Catabolic in nature
Increases transport of amino acids into hepatic
cells
Increases breakdown of proteins into amino
acids for use in gluconeogenesis
Increases conversion of amino acids into
glucose precursors
Other Hormones Affecting Blood Glucose:
Catecholamines
Epinephrine and norepinephrine
Help to maintain blood glucose levels
during periods of stress
Growth hormone
Increases protein synthesis in all cells of
the body, mobilizes fatty acids
from adipose tissue, and antagonizes the effects
of insulin
Glucocorticoids
Critical to survival during periods of
fasting and starvation
Stimulate gluconeogenesis by the liver
Counter regulatory Hormones:
Oppose insulin effects & increase blood
glucose levels
Stimulate glucose production & output
by liver
Decreased movement of glucose into
cells
 Glucagon
Epinephrine
Growth hormone
Cortisol
Diabetes Mellitus:
Prediabetes: impaired fasting plasma glucose
and impaired glucose tolerance
Disorder of carbohydrate, protein, and fat
metabolism
Results from an imbalance between
insulin availability and insulin need
Can represent:
An absolute insulin deficiency
Impaired release of insulin by the
pancreatic beta cells
Inadequate or defective insulin
receptors
Production of inactive insulin or insulin
that is destroyed before it can
carry out its action
Disorder of carbohydrate, protein and fat
metabolism
Imbalance in insulin availability and insulin
need
When uncontrolled glucose can not enter cells
 hyperglycemia and cellular “starvation”
Environmental factors/infections/stress
Cellular dehydration and cellular starvation
Types of Diabetes:
Type 1 results from:
Loss of beta cell function
An absolute insulin deficiency
Subdivisions of Type 1 Diabetes:
Type 1A: Immune mediated
diabetes
Type 1B: Idiopathic diabetes
Type 2 results from:
Impaired ability of the tissues to use
insulin
A relative lack of insulin or impaired
release of insulin in relation to
blood glucose levels
Factors Involved in the Development of Type 1A
Diabetes:
Genetic predisposition (diabetogenic genes)
A hypothetical triggering event that involves an
environmental agent that incites an immune
response
Immunologically mediated beta cell destruction
Idiopathic Type 1B Diabetes:
Those cases of beta cell destruction in which no
evidence of autoimmunity is present
Only a small number of people with type 1
diabetes fall into this category; most are of
African or Asian descent
Type 1B diabetes is strongly inherited
People with the disorder have episodic
ketoacidosis due to varying degrees of insulin
deficiency with periods of absolute insulin deficiency
that may come & go
Syndrome X Metabolic Syndrome:
Risk of developing Type 2 DM
High triglycerides
Fasting plasma glucose >100
Low HDL’s/ may have high LDL’s
Hypertension
Macrovascular disease arteriosclerosis, CAD,
peripheral vascular disease
Insulin resistance
Central obesity/visceral obesity “diabesity”—
prone to Type 2 diabetes
Adipoectin fat cells/increase insulin resistance
Rx: Weight reduction/exercise, prevention
Metabolic Abnormalities Contrbuting to
Hyperglycemia in Typa 2 Diabetes:
Impaired beta cell function and insulin
secretion
Peripheral insulin resistance
Increased hepatic glucose production
Causes of Beta Cell Dysfunction in Patients with
Diabetes:
An initial decrease in the beta cell mass
Increased beta cell apoptosis/decreased
regeneration
Long standing insulin resistance leading to beta
cell exhaustion
Chronic hyperglycemia can induce beta cell
desensitization (‘glucotoxicity’)
Chronic elevation of free fatty acids can cause
toxicity to beta cells (‘lipotoxicity’)
Amyloid deposition in the beta cell can cause
dysfunction
Action of Free Fatty Acids:
Acutely, FFAs act at the level of the beta cell to
stimulate insulin secretion, which, with excessive and
chronic stimulation causes beta cell failure
(‘lipotoxicity’)
FFAs act at the level of the peripheral tissues to
cause insulin resistance and glucose
 underutilization by inhibiting glucose uptake and Intermediate acting
glycogen storage through a reduction in muscle Long acting
glycogen synthetase activity
The accumulation of FFAs and triglycerides Acute Complications of Diabetes:
reduce hepatic insulin sensitivity, leading to Diabetic ketoacidosis fruity breath
increased hepatic glucose production and Precipitated by infection, emotional/
hyperglycemia, especially fasting plasma glucose physical stress in Type 1
levels Increased ffa > ketone
production/ketoacids >metabolic acidosis
Risk Factors of Gestational Diabetes: Causes: too much sugar, not enough
Family history of diabetes insulin, illness/stress, may be initial dx
Glycosuria Hyperglycemia/ketosis/metabolic
History of stillbirth or spontaneous abortion acidosis
Fetal anomalies in a previous pregnancy Hyperosmolar hyperglycemic state
Previous large or heavy for date baby Hyperglycemia (blood glucose >600
Obesity mg/dL)
Advanced maternal age Hyperosmolarity (plasma osmolarity
Five or more pregnancies >310 mOsm/L)
The Three Poly’s of Diabetes: Dehydration
Polyuria: Excessive urination The absence of ketoacidosis
Polydipsia: Excessive thirst Depression of the sensorium
Polyphagia: Excessive hunger Hypoglycemia
Other Symptoms of Hyperglycemia: Increased resistance to the effects of
Weight loss, recurrent blurred vision, fatigue, insulin
paresthesias, skin infections Excessive carbohydrate intake
Major Metabolic Derangements in DKA:
Blood Tests: Hyperglycemia
Fasting Blood Glucose Test Ketosis
Casual Blood Glucose Test Metabolic acidosis
Capillary Blood Tests and Self Monitoring of Definitive Diagnosis of DKA:
Capillary Blood Glucose Levels Hyperglycemia (blood glucose levels >250
Glycated Hemoglobin Testing A1C mg/dL)
Hemoglobin usually does not contain Low bicarbonate (<15 mEq/L)
glucose upon release from bone Low pH (<7.3)
marrow Ketonemia (positive at 1: 2 dilution)
The rate that glucose attaches to Moderate ketonuria
hemoglobin depends on glucose level
Provides an index of glucose levels over Factors Precipitating an Insulin Reaction in Type 1
past 6 12 weeks Diabetes:
Treatment Plans for Diabetes: Error in insulin dose
Nutrition therapy Failure to eat
Exercise Increased exercise
Anti diabetic agents Decreased insulin need after removal of a stress
situation
Oral Anti diabetic Agents: Medication changes
Sulfonylureas Change in insulin site
Repaglinide and nateglinide Alcohol
Biguanides
α Glucosidase Inhibitors Insulin “Shock” Hypoglycemia:
Thiazolidinediones Blood glucose less than 53 mg/dl; most
Three Principal Types of Insulin: common in Type 1
Short acting Caused by: too much insulin, not enough food,
 exercise, vomiting, peak of insulin without Prevent lows in order to prevent Somogyi
sugar, meds, “tight control,” alcohol
Symptoms—hypoglycemia unawareness…h/a, Summary:
hunger, anxiety, drowsiness, sweatiness, Regulating Blood sugar
agitation, tremors, poor insight into lows Types of Diabetes
Rapid onset of manifestations reflect glucose Acute complications
needs of the nervous system Osmolarity thickness of the blood, HHS
Parasympathetic stimulation—sympathetic Kussmaul breathing & fruity breath
response anxiety, sweating, constriction of vessels, DKA
cool clammy skin Chronic complications
Microalbumiuria albumin in the urine,
Chronic Complications of Diabetes: nephropathy
Disorders of the microvasculature Extremity numbness & tingling
Neuropathies: peripheral nerves – pretty neuropathy
sure she asks about neuropathies as a Cell cycles & stages
chronic complication Stem Cells
Nephropathies: kidneys Unipotent
Retinopathies: eyes Olipotent
Distal symmetric neuropathy and foot Pluripotent
ulceration Benign & malignant tumors
Macrovascular complications Osteoma B
Sacoma M
Peripheral Neuropathy: Papillomas
Any primary disorder of the peripheral nerves Adenoma
Results Gleblastoma
Muscle weakness, with or without Lipoma
atrophy and sensory changes Want on meninges of brain & can get to
Involvement without cutting thru tissue, benign
Can involve a single nerve Layers are the maters (PAD)
(mononeuropathy) or multiple nerves Carcinogens: smoking, nitrites
(polyneuropathy) Oncogenes (viral carcinogens) HIV, HPV
Mutagenic
Pathologic Changes Observed with Diabetic Peripheral Obstruction
Neuropathies: Bladder distension
Thickening of the walls of the nutrient vessels Frequency
that supply the nerve Overflow incontinence
Leading to the assumption that vessel jaundice
ischemia plays a major role in the Biopsy
development of neural changes Cancer cachexia
Segmental demyelinization process that affects Tissue integrity
the Schwann cell
Accompanied by a slowing of nerve conduction 4/21/10
Intro CNS, Neurobiology of Psychological Disorders
Somogyi Effect:
“Hypoglycemia begets hyperglycemia” History:
Counterregulatory hormones secreted after Psychology:
insulin induced hypoglycemia careful titration of Psychiatry:
insulin and carbs Neurology:
In addition insulin resistance develops School of Though on Mental Disease:
May be combined with Dawn phenomenon Biologic psychiatry
(increase in GH) between 5 to 9 am  Mental disorders are due to anatomic,
hyperglycemia developmental, and functional disorders
 of the brain Memory and nonverbal memory
Psychosocial psychiatry Concept formation
Mental disorders are due to impaired Functions of the Occipital Lobe:
psychological development, a Vision
consequence of poor child rearing or Possible information holding area
environmental stress Learning & Memory (thoughts):
Nature vs. nurture: Thought processes involve patterns of stimuli
Adopted twin studies from many parts of the nervous system
Neuroimaging studies simultaneously.
Mental Illness: Cerebral cortex
Most likely occurs as the result of Thalamus
Genetic factors Limbic system
Environmental factors Reticular formation
Substance abuse Memory traces
A combination of all 3 New or reactivated pathways transmit
Heredity in Mental Illness: neural circuits
Complex influences of genetic and Limbic System:
environmental factors on neural development and Emotional behavior
function Includes several structures deep within the
Nurture versus nature brain
Genetic vulnerability and environmental Includes among others hippocampus &
influences play significant roles in the amygdala
development of mental illness. Emotional behavior
Other factors are involved Emotional memory
Behavioral Anatomy of the Brain: Hippocampus short term memory
Cortex, thalamus, prefrontal cortex, frontal hippocampal atrophy Alzheimer’s
lobe, temporal lobe, parietal lobe, occipital Amygdala modulation of social responses ie
lobe, limbic association area, prefrontal association fear, aggression, sexual
area Origin of the Manifestations of Mental Illness:
Functions of the Frontal Lobe: Alterations in brain neuron functioning
Abstract vs. concrete reasoning Destruction of those neurons
Motivation/volition Alterations in the neural connections among the
Concentration brain regions
Decision making Steps of Neurotransmission:
Purposeful behavior Synthesis of a transmitter substance
Memory, sequencing, making meaning of Storage and release of the transmitter
language Binding of the transmitter to receptors on the
Speech organization and production postsynaptic membrane
Aspects of emotional response Removal of the transmitter from the synaptic
Functions of the Temporal Lobe: cleft
Visual spatial recognition Neuromediators (neurotransmitters):
Attention Acetylcholine
Motivation Dopamine
Emotional modulation and interpretation Norepinephrine & epinephrine
Impulse and aggression control Serotonin
Interpretation and meaning of social contact γ aminobutyric acid, glutamate, aspartate, and
Aspects of sexual action and meaning glycine
Functions of Parietal Lobe:
Sensory integration and spatial relations Schizophrenia:
Bodily awareness Chronic, debilitating psychotic disorder that
Filtration of background stimuli involves the disconnection between thought
Personality factors and symptom denial and language
 Affects the thinking, feeling, perceiving, (haloperidol), and thioxanthenes
behaving, and experiencing the environment (chlorprothixene)
Onset between 17 and 25 years Atypical antipsychotics
Men and women seem to be affected equally Exemplified first by clozapine, are more
First degree relatives of a person with effective in treating the negative
schizophrenia have a 10 fold greater prevalence symptoms of schizophrenia and produce fewer
of the illness extrapyramidal effects
Manifestations of Schizophrenia: Diagnosis of Schizophrenia:
Negative symptoms: Two or more of the following symptoms must
Reflect the absence of normal social and be present for a significant portion of 1
interpersonal behaviors month:
Absence of normal social and Delusions
interpersonal behaviors Hallucinations
Alogia Disorganized speech
Avolition Grossly disorganized or catatonic
Apathy behavior
Affective flattening Negative symptoms
Anhedonia One or more areas of functioning must be
Blunted response to pain significantly impaired and continuous signs of
Positive symptoms: the disturbance must persist for at least 6 months
Reflect the presence f abnormal Goals of Treatment for Schizophrenia:
behaviors Initially the goal may be primarily to reduce
Incomprehensible speech agitation and the risk of physical harm
Delusions Induce a remission
Hallucinations Prevent a recurrence
Catatonic behavior Restore behavioral, cognitive, and psychosocial
Enhancement or a blunting of the senses function to premorbid levels
Sensory overload due to loss of the Neuroimaging Studies:
ability to screen external sensory Imaging studies do not generally diagnose
stimuli mental illness, but do suggest a brain based
Disorders of Perception: problem
Hallucinations:
Sensory perceptions that occur without Mood Disorders:
external stimulation of the Depression: a mental state characterized by a
relevant sensory organ pessimistic sense of inadequacy and a despondent
Visual, auditory, tactile, olfactory lack of activity
Can occur with: Mania: characterized by extremely elevated
Epilepsy, tumors, metabolic, mood, energy, and unusual thought patterns
substance withdrawal, a variety of Affective disorders
psychiatric disorders Affect approximately 21% of the
Delusions: population
Characterized by a false belief and the Women affected twice as often as men
persistent, unshakable acceptance 20–40% of adolescents who present
of the false belief with major depression develop
Types of delusions: bipolar disorder within five years
Persecution, influence, ill health, Classification of Major Depression:
grandeur, poverty, possession Unipolar:
Major Groups of Antipsychotic Agents for Characterized by a persistent unpleasant
Schizoprhenia: mood
Typical antipsychotics Bipolar:
Include the phenothiazines Characterized by alternating periods of
(chlorpromazine), butyrophenones depression and mania
Characteristics of Depression:
Depressed mood
Anhedonia (inability to experience pleasure)
Feelings of worthlessness or excessive guilt
Decreased concentration
Psychomotor agitation or retardation
Insomnia or hypersomnia
Decreased libido
Change in weight or appetite
Thoughts of death or suicidal ideation
Depression Pathophysiology:
Dysregulation of amine neurotransmitters in the
brain (DA, NE, 5HT)
Brain is “predisposed” to depressive response,
which is triggered initially by a stressful
life event, illness, or drug exposure
Those not predisposed have milder, more
transient dysphoria to these triggers
Diagnosis of Depressive Disorders:
Simultaneous presence of five or more of the
symptoms during a 2 week period.
Differentiated from grief reactions,
medication side effects, and sequelae of
medical illnesses
Bipolar disorder is diagnosed on the basis of
the pattern of occurrence of manic,
hypomanic, and depressed episodes
Bipolar Disorder:
Mania: mood is high for at least a week,
impaired judgment, impaired social function,
begins abruptly and escalates. If severe may have
psychoses, intermittent depression
Hypomania: less severe symptoms, can
function
Affects 1% to 2% of the population
Significant genetic risk
80% to 90% of patients have a relative
with mood disorder
80% concordance with identical twin
Age at onset is about 20; if older than 40
probably something else
First episode usually precipitated by life event
Treatment for Unipolar & Bipolar Illnesses:
Antidepressant drugs
Electroconvulsive therapy
Lithium
Anticonvulsants
Psychotherapy
Anxiety Disorders:
25% of the population is affected by anxiety
disorders (a lot to be anxious about in today’s
society)
Anxiety disorders contribute to increased risk
of GI, CV disease and stroke
Anxiety disorders can impair workplace
performance
Social anxiety
Generalized anxiety
Panic disorder
Post traumatic stress disorder (PTSD)
Obsessive compulsive disorder (OCD)
Specific phobias
Pathophysiology of Anxiety:
Experience a level of “fight or flight” on a
persistent basis. Overactivity of NE in low level
threat situations
Brainstem NE neurons from the locus coeruleus
are hyperactive, possibly secondary to
deficient 5HT or GABA regulation of NE (and
DA) release
Effective drug therapy increases GABA or 5HT
Effects of Chronic Stress:
Pathophysiologic changes occur
Altered function occurs
A component of the system fails
Neural and hormonal connections
among components of the system are
dysfunctional
The original stimulus for the activation
of the system is prolonged
PTSD:
Chronic activation of the stress response as a
result of experiencing a potentially life
threatening event
Formerly called battle fatigue or shell shock
because it was first characterized in men and
women returning from combat
Caused by major catastrophic events
Major weather related disasters, airplane
crashes, terrorist bombings, and
rape or child abuse
Characteristics of PTSD:
Intrusion: the occurrence of “flashbacks”
during waking hours or nightmares in which the
event is relived, often in vivid and frightening
detail
Avoidance: the emotional numbing that
accompanies this disorder and disrupts important
personal relationships
Hyperarousal: the presence of increased
irritability, difficulty concentration, an
exaggerated startle reflex, and increased
vigilance and concern over safety
Substance Abuse:
Repeated use of alcohol or other drugs resulting
in functional problems
Addiction usually describes a combination of
craving, compulsive use, and high risk of
relapse after withdrawal
Addiction Disorders:
14.6% of the U.S. adult population have
substance abuse disorders.
Addictions account for an estimated
8.5% of these numbers.
Multifactorial vulnerability
Genetic disposition, environmental
factors, and physiologic mechanisms
resulting from repeated drug use
It has been suggested that self
medication of symptoms associated with
psychiatric disorders underlies addiction
Neurophysiologic Basis of Addiction:
Mesolimbic dopamine system
Functions as a gate that regulates
biological drives and motivation
Alteration in levels of dopamine
Pathway
Nucleus accumbens
Striatum of the basal ganglia
Frontal cortex
Treatment of Addiction:
Biologic, behavioral, and psychosocial
interventions
Medications
Methadone: opiate addiction
Buprenorphine: opiate addiction
Naltrexone: alcohol and opiate
addiction
Brain Functions & Addictions:
Locus ceruleus superior angle of the floor of
the brain
Ventral Tegmental Area (VTA) neurons project
to the nucleus accumbens (NAc)
Drugs of abuse activate release of dopamine
Drugs that stimulate dopamine receptors D1 &
D2 induce relaps
Cause & Effects of addictions:
Cocaine  stroke
Ecstasy & others  neuroimaging
Neurotransmitters
Traumatic life events  substance
abuse  negative social impact
Dementia:
Impairment of short and long term memory,
associated with abstract thinking, impaired
judgment, other higher cortical functions, or
personality change
Caused by any disorder that permanently
damages large association areas serving
memory and learning
Diagnosis
Assessment, History, Complete
physical, Cognition, Functional status
Laboratory and imaging studies
Differentiate between Types of Dementia:
Alzheimer’s disease: beta plaques & tangles,
hippocampal atrophy
Vascular Dementia
Pick’s Disease: FTD, semantic dementia
Creutzfeldt Jakob Disease: variant of mad cow
disease (prion proteins)
Wernicke Korsakoff Syndrome: B vitamins get
destroyed, alcohol
Huntington’s Disease: single gene Autosomal
dominant disorder
Alzheimer’s Histology:
Neuritic (senile) plaques, neurofibrillary
tangles, amyloid angiopathy
Stages of Alzheimer Disease:
Initial change is subtle
Short term memory loss
Mild changes in personality
Randomly forget important and
unimportant details
Moderate stage
Global impairment of cognitive
functioning
Changes in higher cortical functioning
needed for language, spatial
relationships, and problem solving;
disorientation, lack of insight, and
inability to carry out the activities of daily
living, extreme confusion
Severe Alzheimer disease is the last stage of the
disease
Loss of ability to respond to the
environment
Require total care
Bedridden
Death can occur as a result of complications
related to chronic debilitation
Wernicke Disorders:
Wernicke Korsakoff syndrome
Chronic alcoholism
Wernicke disease
Weakness
 Paralysis
Nystagmus
Ataxia
Confusion
Peripheral neuropathy
Unsteady gait
Diplopia
Nutritional cause
Deficiency of thiamine
Interferes with production of glucose

Which of the following conditions can be experienced

normally, but if length of time increases, becomes
a disorder? depression
Which lobes of brain major role in decision making?
frontal
Endocrine disorders primary, secondary, tertiary
Hypopituitarism, hyperpituitarism
Growth hormone deficiency
Hyper vs. hypothyroidism
Graves disease: genetic, exopthalamus
Thyroid storm
Adrenal Coritcal Insufficiency
Cushing syndrome
Addisons disease
Adrenal hyperplasia
Malignant vs benign tumors
Common cancers men vs women
In situ
Cachexia
Neoplasm
S&S of urinary outflow obstruction & urine retention
Stem cells unipotant, olgipotent, pluripotent
Carcinogens, oncogenes, mutogenic, obstruction
Bladder distention
Frequency
Overflow incontinence
Jaundice
Biopsy
Paraneoplastic
Viral carconogens vs oncogenic viruses
Manifestations of cancer cachexia, paraneoplastic
syndromes, tissue integrity
Glioblastoma. Meningioma, sarcome, melamoma
Differentiate tumor makers from oncogenes &
carcinogens