NURS 241 Exam 3Endocrine Disorders

Endocrine Systems:– Intercellular communication network– Hormones travel from cell to cell through the

bloodstream.– Regulates complex phenomena

• Stress response• Growth and development• Fluid and electrolyte balance• Reproduction

Functions of the Endocrine System:– Growth and development– Sex differentiation– Metabolism– Adaptation to an ever changing environment

• Regulation of digestion• Use and storage of nutrients• Electrolyte and water metabolism• Reproductive functions

Hormones:– Function as chemical messengers

• Move through the blood to distant target sites of action

• Can also act more locally as paracrine or autocrine messengers that incite more local effects

• Most are present in body fluids at all times in greater or lesser amounts as needed

– Characteristics• A single hormone can exert various effects

in different tissues• A single function can be regulated by

several hormones

Categories of Hormones According to Structure:– Amines and amino acids– Peptides, polypeptides, proteins & glycoproteins– Steroids– Fatty avid derivative

Solubility of Hormones Determines Mechanism of Actions:– Lipid soluble hormones

• Steroid• Thyroid

– Water soluble hormones• Proteins and peptides• Catecholamines

Factors Affecting Response of a Target Cell to a Hormone:– Number of receptors present

• Up regulation• Down regulation

– Affinity of these receptors for hormones• Affected by a number of conditions• Example: the pH of the body fluids plays an

important role in the affinity of insulin receptorsControl of Hormone Levels:– Affected by diurnal fluctuations that vary with

the sleep–wake cycle• Growth hormone (GH) and

adrenocorticotropic hormone (ACTH)– Secreted in a complicated cyclic manner

• Female sex hormones– Regulated by feedback mechanisms that

monitor substances such as glucose (insulin) and water (ADH) in the body

– Regulated by feedback mechanisms that involve the hypothalamic pituitary target cell system

Negative Feedback:– Feedback signals decrease secretion by

• Down regulation of receptor number• Decreased sensitivity of receptors• For example, thyroid hormone down regulates

TRH receptors on thyrotroph cells in the pituitary

Feedback Loops:– Ultra short loop

• Within the hypothalamus– Short loop

• From pituitary to hypothalamus– Long loop

• From target organ to hypothalamus & pituitary

Categories or Disturbances of Endocrine Function:

– Hypofunction : underproduction of hormone • Causes:

- Congenital defects- Disruption in blood flow, infection,

inflammation, autoimmune responses, or neoplastic growth

- Decline in function with aging- Atrophy as the result of drug therapy or

unknown reasons- Receptor defects

• Etiology:- Autoimmune inhibition

- Nonsecreting tumors- Surgical removal- Ischemia, infarct- Receptor defects

• Treatment:- Hormone therapy

– Hyperfunction : excessive hormone production• Causes:

- Excessive stimulation and hyperplasia of the endocrine gland

- Hormone producing tumor of the gland• Etiology:

- Autoimmune stimulation- Secreting tumors- Idiopathic

• Treatment:- Surgical removal- Blocking drugs- Irradiation

Categories of Endocrine Disorders:– Primary Disorders:

• Originate in the target gland responsible for producing the hormone

– Secondary Disorders :• The target gland is essentially normal, but its

function is altered by defective levels of stimulating hormones or releasing factors from the pituitary system

– Tertiary Disorders: • Result from hypothalamic dysfunction • Both the pituitary and target organ are

understimulated

Primary vs. Secondary Disorders:– Primary disorders are due to dysfunction of the

target gland– Secondary disorders are due to dysfunction of

the pituitary gland– Primary and secondary disorders can be

differentiated by looking at feedback loops

Categories of Pituitary Tumors:– Primary tumors – Secondary tumors

• Metastatic lesions– Functional tumors

• Secrete pituitary hormones – Nonfunctional tumors

• Do not secrete hormonesManifestations of Hypopituitarism:

– Usually occur gradually– Can present as an acute and life threatening

condition– Symptoms:

• Being chronically unfit• Weakness and fatigue• Loss of appetite• Impairment of sexual function• Cold intolerance

Measurement of Hypothalamin Pituitary Target Cell Hormones:– Serum cortisol– Serum prolactin– Serum thyroxine and TSH– Serum testosterone (male)/serum estrogen

(female) and serum LH/FSH– Serum GH/insulin like growth factor 1– Plasma osmolality and urine Osmolality

Hormones Essential for Normal Body Growth & Maturation– Growth hormone (GH)– Insulin– Thyroid hormone– Androgens

Growth Hormone:– Produced by somatotropes in the anterior

pituitary– Necessary for linear bone growth in children– Stimulates cells to increases in size and divide

more rapidly– Enhances amino acid transport across cell

membranes– Decreases the rate at which cells use

carbohydrates

Growth Hormone in Children– GH deficiency:

• Interferes with linear bone growth• Results in short stature or dwarfism

– GH excess:• Results in increased linear bone growth• Gigantism

Effects of Growth Hormone Excess in Adults:– Overgrowth of the cartilaginous parts of the

skeleton– Enlargement of the heart and other organs of the

body

– Metabolic disturbances resulting in altered fat metabolism and impaired glucose tolerance

Causes of Short Stature:– Variants of normal– Low birth weight– Chronic illness and malnutrition– Functional endocrine disorders– Chromosomal disorders– Skeletal abnormalities– Unusual syndromes– Genetic short stature:

• Well proportioned and have a height close to the midparental height of their parents

– Constitutional short stature:• Moderately short stature, thin build, delayed

skeletal and sexual maturation, and absence of other causes

of decreased growth– Protein calorie malnutrition– Chronic diseases

• End stage renal disease • Poorly controlled diabetes mellitus

– Malabsorption syndromes– Excessive glucocorticoid administration– Emotional disturbances

Tall Stature:– Constitutional tall stature

• A child who is taller than his or her peers and is growing at a velocity that is within the normal range for bone age

– Genetically tall– Other causes

• Marfan syndrome: genetic condition that results in rapid bone growth and late/absence of epiphyseal capping

• Endocrine causes Sexual precocity: early onset of

estrogen and androgen secretion and excessive GH

Growth Hormone:– Secreted from anterior pituitary somatotrophs in

response to increased GHRH and decreased somatostatin

– GH is secreted in pulses with most secretion during sleep

– 191 amino acid peptide with a circulatory T1/2 of 20 min

– Somatomedins have T1/2 of 20 hr

Altered GH Secretion:– Too much GH

• Children tall stature• Adults acromegaly

– Too little GH• Children short stature• Adult decreased muscle?

Evaluation of Short Stature:– Routine assessment of height and weight

• Plot on growth curve• Watch for “falling off the curve”• Often occurs in later childhood or puberty

– Assess parental height– Inquire about parental and sibling growth

pattern—delayed puberty?Differential Diagnosis of Short Stature:– Constitutional (normal)– Delayed puberty– Pituitary failure (1:4000 children)

• Isolated GH deficiency• Multiple anterior pituitary hormones

– Other• Chronic disease, Turner syndrome,

malnutrition, bone disease, etc.Diagnostic Testing:– Evaluation of bone age

• Refer for radiologic exam of epiphyseal plate

– Growth hormone assay– Growth hormone provocation tests

• Arginine, hypoglycemiaAcromegaly:– When GH excess occurs in adulthood or after epiphysis of long bones have fused GH secreting pituitary adenoma

• Headache, visual disturbances• Hyperglycemia “diabetogenic”• Increased lean body mass

Bone and soft tissue– Treatment:

• Hypophysectomy• Irradiation

– Treatment Goals:• Normalization of the GH response to an oral

glucose load• Normalization of IGF 1 levels to age and

sex matched control levels• Removal or reduction of the tumor mass• Relieving the central pressure effects• 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

responsivenessManifestations 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

– Fine needle aspiration (FNA) biopsy of a thyroid nodule

Graves Disease:– State of hyperthyroidism, goiter and

ophthalmopathy (less commonly, dermopathy)– An autoimmune disorder characterized by abnormal

stimulation of the thyroid gland by thyroid stimulating antibodies (thyroid stimulating immunoglobulins [TSI]) that act through the normal TSH receptors

– Is associated with human leukocyte antigen (HLA) DR3 and HLA B8

– Familial tendency is evident

Pathophysiology:– Etiology: autoimmune

• High association with HLA D3 and B8• Women affected more often than men 8:1

– Pathogenesis• IgG autoantibodies bind to and stimulate TSH

receptors on thyroid.• Thyroid hyperplasia and hypersecretion result.

– Exophthalmos due to IgG

Treatment:– RAIU ablation– Symptom control with blockers– PTU and thyroxine to inhibit synthesis

• Thyroxine may reduce relapse, which often occurs with PTU alone.

– Surgery

Manifestations of Thyroid Storm:– Very high fever– Extreme cardiovascular effects

• Tachycardia, congestive failure, and angina– Severe CNS effects

• Agitation, restlessness, and delirium– **High mortality rate**

Steroid Hormones Produced by the Adrenal Cortex:– Mineralcorticoids (aldosterone)

• Function in sodium, potassium, and water balance

– Glucocorticoids (cortisol)• Aid in regulating the metabolic functions of the

body and in controlling inflammatory response• Essential for survival in stress situations

– Adrenal sex hormones (androgens) • Serve mainly as source of androgens for

women

Actions of Cortisol:– Glucose metabolism– Protein metabolism– Fat metabolism– Anti inflammatory action– Psychic effect– Permissive effect

Clinical Findings of Adrenal Insufficiency:– Anorexia and weight loss– Fatigue and weakness– Gastrointestinal symptoms, nausea, diarrhea– Myalgia, arthralgia, abdominal pain– Orthostatic hypotension– Hyponatremia– Hyperkalemia– Hyper pigmentation– Secondary deficiency of select hormones– Associated autoimmune conditions

Stages of Adrenal Cortical Insufficiency:– Primary adrenal cortical insufficiency (Addison’s

disease)– ACTH levels are elevated because of lack of

feedback inhibition– Secondary adrenal cortical insufficiency

• Occurs as a result of hypopituitarism or because pituitary gland has been surgically removed

– Acute adrenal crisis- ***Life threatening situation occurs***

Glucocorticoid Hormone Excess:– Cushing syndrome (hypercortisolism) know

symptoms• Pituitary form results from excessive production

of ACTH by a tumor of the pituitary gland • Adrenal form caused by a benign or malignant

adrenal tumor • Ectopic form, nonpituitary ACTH secreting

tumor• Altered fat metabolism • Muscle weakness• Muscle wasting• Purple striae• Osteoporosis • Derangements in glucose metabolism • Hypokalemia • 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 metMechanisms 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 originatedTypes 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 surfaceFactors 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 originCharacteristics 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 tissueMetastasis:

Spread of a malignant tumor to a distant siteMethods by Which Cancer Spreads:

Direct invasion and extension Seeding of cancer cells in body cavities Metastatic spread through the blood or lymph

pathwaysFactors 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 producedSteps Involving the Transformation of Normal Cells into Cancer Cells:

Initiation Cells exposed to doses of carcinogenic

agents making them susceptible to malignant transformation

Promotion:

Unregulated accelerated growth in already initiated cells caused by various chemicals and growth factors

Progression: Tumor cells acquire malignant

phenotypic changes that promote invasiveness, metastatic competence,

autonomous growth tendencies, and increased karyotypic instabilityHost & Environmental Factors Leading to Cancer:

Obesity Heredity Hormones Carcinogens

Chemical Radiation

Oncogenic viruses Immunologic mechanisms

Genes that Control Cell Growth & Replication: Proto oncogenes Tumor suppressor genes Genes that control programmed cell death or

apoptosis Genes that regulate repair of damaged DNA

Genetic Bases of Cancer: Cancer is caused by genetic mutations Two important classes of genes are involved Overactivity of proto oncogenes Inactivation of tumor suppression genes (anti

oncogenes)Proto Oncogenes Code For:

Growth factors Growth factor receptors Intracellular pathway components Transcription factors Overactivation proliferation

Tumors Suppression Genes Inhibit Cell Replication: pRB: master brake of the cell cycle, inhibits

transcription TP53: suicide gene, causes apoptosis of errant

cellsChemical Carcinogens:

Thousands of natural and man made substances are mutogenic.

Exposure through inhalation, topical contact, or ingestion

Asbestos mesothelioma Vinyl chloride liver cancer Napthylamine bladder cancer

Host & Environmental Factors Leading to Cancer: Carcinogens

Food fried in reused fat Alcohol Nitrites Plastic and chemicals Lack of antioxidants

Clinical Manifestations of Cancer: Cancer Cachexia

Weight loss and wasting of body fat and muscle tissue; profound weakness, anorexia, and anemia

Paraneoplastic Syndromes Manifestations in sites not directly

affected by the disease Tissue Integrity

Compressed and eroded blood vessels, ulceration and necrosis, frank

bleeding, and hemorrhageDiagnostic Measures for Cancer Detection:

Pap smear Biopsy Tumor markers

Antigens on surface of tumor or Released from normal cells in response

to the presence of a tumor Present in benign conditions Not elevated in early stages of

malignancy CA 125 & PSA

Staging and grading of tumorsGoals of Cancer Treatment:

Curative, control, palliativeHow Do Benign & Malignant Tumors Differ?

Benign: OMA Strictly local, no metastasis, well

differentiated Malignant: SARCOMA

Invasive, metastatic potential, rapidly growing, anaplasticStaging & Grading of Tumors:

Staging: according to clinical spread description of location and spread of

tumors in the body T: tumor (size, local, or invasive) N: nodes (no, yes, distant) M: metastasis (no, yes)

Grading: according to histologic or cellular characteristics

Histologic analysis of degree of anaplasiaCancer Treatment Modalities:

Surgery, radiation, hormonal therapy, targeted therapy

Biotherapy Immunotherapy: changing the person’s

own immune response to cancer Biologic response

Chemotherapy Direct DNA interacting Indirect DNA interacting Cell cycle specific Cell cycle noonspecific

What Side Effects Are Likey to Occur in Persons Receiving Radiation or Chemo?

Bone marrow depression: anemia, thrombocytopenia, leukopenia

Mucosal sloughing and alopecia Pain, nausea

Stem Cell Transplantation: Bone marrow transplantation (BMT) Peripheral blood stem cell transplantation

(PBSCT) Two treatment approaches for

individuals with leukemias, certain solid tumors, and other cancers previously thought to

be incurableTypes of Surgery for Cancer:

Cryosurgery: instilling liquid nitrogen into the tumor through a probe

Chemosurgery: using corrosive paste with multiple frozen sections to ensure complete removal of tumor

Laser surgery: using a laser beam to resect tumor

Laparoscopic surgery: performing surgery through two small incisionsCancer Routinely Screened:

Breast (clinical breast exam and mammogram) Uterine (clinical palpation for size,

irregularities) Cervical (speculum exam and Pap smear) Skin (visual inspection) Lymphomas (palpation of lymph nodes) Prostate (digital rectal examination, PSA

testing) Testicular (palpation) Leukemia (complete blood cell count) Colorectal (fecal occult blood, colonoscopy

Common Solid Tumors of Childhood: Brain and nervous system tumors Neuroblastoma Wilms’ tumor Rhabdomyosarcoma and embryonal sarcoma Retinoblastoma Osteosarcoma

Ewing’s sarcomaCharacteristics of Childhood Cancer:

Most involve the hematopoietic system, nervous system, or connective tissue

Heritable forms of cancer tend to have: An earlier age of onset A higher frequency of multifocal lesions

in a single organ Bilateral involvement of paired organs

or multiple primary tumorsObstruction:

Blockage of any hollow tubular structure that prevents normal passage

Airways, blood vessels, GI tract, biliary ducts, Eustachian tube, brain/CSF, urethra/ureters, lymph vessels, sinuses, glandsSigns of Outflow Obstruction & Urine Retention:

Bladder distention Hesitancy Straining when initiating urination Small and weak stream Frequency Feeling of incomplete bladder emptying Overflow incontinence

Causes of Pancreatic Cancer: The cause of pancreatic cancer is unknown Smoking appears to be a major risk factor The second most important factor appears to be

diet Increasing total calorie intake High intake of fat, meat, salt,

dehydrated foods, fried foods, refined sugars, soy beans, and nitrosaminesManifestations of Liver Failure:

Hematologic disorders Endocrine disorders Skin disorders Hepatorenal syndrome Hepatic encephalopathy

Acid Base Balance

Acid Base Balance: Metabolic activities require precise acid base

balance, which is reflected in the pH of extracellular fluids

Acid: a molecule that can release hydrogen ion (H+)

Base: a molecule that can accept or combine with a hydrogen ion (H+)

H2CO3: Carbonic Acid CO2: Carbon Dioxide

HCO3: BicarbonateFactors 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 7.45pH Buffering:

H+ + HCO3 H2CO3 CO2 + H2O Kidneys regulate bicarbonate Lungs regulate carbon dioxide

One system can compensate for the other to keep ratio near 20:1Arterial Blood Gas Norms:

pH: 7.35 7.45 PaCO2: 35 45 mm Hg HCO3

–: 22 26 mEq/LpH:

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 acidsProcesses Involved in the Regulation of Plasma Concentration of HCO:

Reabsorption of the filtered bicarbonate Generation of new bicarbonate

By excretion of nonvolatile acidsLab 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–

reabsorptionCauses 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 levelsManifestations 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

If no renal disease, decreased H+ excretion and decreased HCO3

– reabsorptionCauses of Metabolic Alkalosis:

Excessive gain of bicarbonate or alkali Excessive loss of hydrogen ions Increased bicarbonate retention Volume contraction

Manifestations of Metabolic Alkalosis: Increase in pH due to a primary excess of

plasma HCO3– ions

Caused by: Loss of H+ ions Net gain in HCO3

Loss of Cl– ions in excess of HCO3–

ionsSigns of Compensation:

Decreased rate and depth or respiration Increased urine H

Respiratory Acidosis: Primary disturbance

Increase in PCO2 Respiratory compensation

None Renal compensation

Increased H+ excretion and increased HCO3

– reabsorptionCauses of Respiratory Acidosis:

Occurs in acute or chronic conditions that impair effective alveolar ventilation and cause an accumulation of PCO2

Impaired function of the respiratory center in the medulla (as in narcotic overdose) Lung disease Chest injury Weakness of the respiratory muscles Airway obstruction

Respiratory Alkalosis: Primary disturbance

Decrease in PCO2 Respiratory compensation

None Renal compensation

Decreased H+ excretion and decreased HCO3

– reabsorptionCauses of Respiratory Alkalosis:

Excessive Ventilation Anxiety and psychogenic

hyperventilation Hypoxia and reflex stimulation of

ventilation Lung disease that reflexively stimulates

ventilation Stimulation of respiratory center Mechanical ventilation

Manifestations of Respiratory Alkalosis: Decrease in PCO2 Deficit in H2CO3

The pH is above 7.45, arterial PCO2 is below 35 mm Hg, and plasma HCO3

– levels usually are below 24 mEq/L (24 mmol/L)

Neural Function Constriction of cerebral vessels and increased neuronal excitability

Cardiovascular function Cardiac dysrhythmias

Compensations: Renal for respiratory imbalances Respiratory or metabolic imbalances

Categories of the Manifestations on Acidosis: S&S of he disorder causing acidosis Changes in body function related to recruitment

of compensatory mechanisms Alterations in cardiovascular, neurologic, and

musculoskeletal function resulting from the decreased pH

Sources of the Body’s Plasma HCO3: CO2 that is produced during metabolic

processes Reabsorption of filtered HCO3

–

Generation of new HCO3– by the kidney

Respiratory Control of pH: Lungs retain or eliminate CO2

CO2 retention decreases pH CO2 elimination increases pH

Renal Control of pH: Kidneys retain or eliminate HCO3

HCO3 retention increases pH

HCO3 elimination decreases pH

Potassium Hydrogen Ion Exchange: Excess H+ in the ECF causes

H+ to move into cells K+ to move out of cells into ECF

Ion Exchange: Acidosis:

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 destructionIdiopathic 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 glycogen storage through a reduction in muscle glycogen synthetase activity

The accumulation of FFAs and triglycerides reduce hepatic insulin sensitivity, leading to increased hepatic glucose production and hyperglycemia, especially fasting plasma glucose levels

Risk Factors of Gestational Diabetes: Family history of diabetes Glycosuria History of stillbirth or spontaneous abortion Fetal anomalies in a previous pregnancy Previous large or heavy for date baby Obesity Advanced maternal age Five or more pregnancies

The Three Poly’s of Diabetes: Polyuria: Excessive urination Polydipsia: Excessive thirst Polyphagia: Excessive hunger

Other Symptoms of Hyperglycemia: Weight loss, recurrent blurred vision, fatigue,

paresthesias, skin infections

Blood Tests: Fasting Blood Glucose Test Casual Blood Glucose Test Capillary Blood Tests and Self Monitoring of

Capillary Blood Glucose Levels Glycated Hemoglobin Testing A1C

Hemoglobin usually does not contain glucose upon release from bone

marrow The rate that glucose attaches to

hemoglobin depends on glucose level Provides an index of glucose levels over

past 6 12 weeksTreatment Plans for Diabetes:

Nutrition therapy Exercise Anti diabetic agents

Oral Anti diabetic Agents: Sulfonylureas Repaglinide and nateglinide Biguanides α Glucosidase Inhibitors Thiazolidinediones 

Three Principal Types of Insulin: Short acting

Intermediate acting Long acting

Acute Complications of Diabetes: Diabetic ketoacidosis fruity breath

Precipitated by infection, emotional/ physical stress in Type 1

Increased ffa > ketone production/ketoacids >metabolic acidosis

Causes: too much sugar, not enough insulin, illness/stress, may be initial dx

Hyperglycemia/ketosis/metabolic acidosis

Hyperosmolar hyperglycemic state Hyperglycemia (blood glucose >600

mg/dL) Hyperosmolarity (plasma osmolarity

>310 mOsm/L) Dehydration The absence of ketoacidosis Depression of the sensorium

Hypoglycemia Increased resistance to the effects of

insulin Excessive carbohydrate intake

Major Metabolic Derangements in DKA: Hyperglycemia Ketosis Metabolic acidosis

Definitive Diagnosis of DKA: Hyperglycemia (blood glucose levels >250

mg/dL) Low bicarbonate (<15 mEq/L) Low pH (<7.3) Ketonemia (positive at 1: 2 dilution) Moderate ketonuria

Factors Precipitating an Insulin Reaction in Type 1 Diabetes:

Error in insulin dose Failure to eat Increased exercise Decreased insulin need after removal of a stress

situation Medication changes Change in insulin site Alcohol

Insulin “Shock” Hypoglycemia: Blood glucose less than 53 mg/dl; most

common in Type 1 Caused by: too much insulin, not enough food,

exercise, vomiting, peak of insulin without sugar, meds, “tight control,” alcohol

Symptoms—hypoglycemia unawareness…h/a, hunger, anxiety, drowsiness, sweatiness, agitation, tremors, poor insight into lows

Rapid onset of manifestations reflect glucose needs of the nervous system

Parasympathetic stimulation—sympathetic response anxiety, sweating, constriction of vessels, cool clammy skin

Chronic Complications of Diabetes: Disorders of the microvasculature

Neuropathies: peripheral nerves – pretty sure she asks about neuropathies as a chronic complication

Nephropathies: kidneys Retinopathies: eyes Distal symmetric neuropathy and foot

ulceration Macrovascular complications

Peripheral Neuropathy: Any primary disorder of the peripheral nerves Results

Muscle weakness, with or without atrophy and sensory changes

Involvement Can involve a single nerve

(mononeuropathy) or multiple nerves (polyneuropathy)

Pathologic Changes Observed with Diabetic Peripheral Neuropathies:

Thickening of the walls of the nutrient vessels that supply the nerve

Leading to the assumption that vessel ischemia plays a major role in the development of neural changes

Segmental demyelinization process that affects the Schwann cell

Accompanied by a slowing of nerve conduction

Somogyi Effect: “Hypoglycemia begets hyperglycemia” Counterregulatory hormones secreted after

insulin induced hypoglycemia careful titration of insulin and carbs

In addition insulin resistance develops May be combined with Dawn phenomenon

(increase in GH) between 5 to 9 am hyperglycemia

Prevent lows in order to prevent Somogyi

Summary: Regulating Blood sugar Types of Diabetes Acute complications

Osmolarity thickness of the blood, HHS Kussmaul breathing & fruity breath

DKA Chronic complications

Microalbumiuria albumin in the urine, nephropathy

Extremity numbness & tingling neuropathy

Cell cycles & stages Stem Cells

Unipotent Olipotent Pluripotent

Benign & malignant tumors Osteoma B Sacoma M Papillomas Adenoma Gleblastoma Lipoma Want on meninges of brain & can get to

without cutting thru tissue, benign Layers are the maters (PAD)

Carcinogens: smoking, nitrites Oncogenes (viral carcinogens) HIV, HPV Mutagenic Obstruction Bladder distension Frequency Overflow incontinence jaundice Biopsy Cancer cachexia Tissue integrity

4/21/10Intro CNS, Neurobiology of Psychological Disorders

History: Psychology: Psychiatry: Neurology:

School of Though on Mental Disease: Biologic psychiatry

Mental disorders are due to anatomic, developmental, and functional disorders

of the brain Psychosocial psychiatry

Mental disorders are due to impaired psychological development, a

consequence of poor child rearing or environmental stress

Nature vs. nurture: Adopted twin studies Neuroimaging studies

Mental Illness: Most likely occurs as the result of

Genetic factors Environmental factors Substance abuse A combination of all 3

Heredity in Mental Illness: Complex influences of genetic and

environmental factors on neural development and function

Nurture versus nature Genetic vulnerability and environmental

influences play significant roles in the development of mental illness.

Other factors are involvedBehavioral Anatomy of the Brain:

Cortex, thalamus, prefrontal cortex, frontal lobe, temporal lobe, parietal lobe, occipital lobe, limbic association area, prefrontal association area

Functions of the Frontal Lobe: Abstract vs. concrete reasoning Motivation/volition Concentration Decision making Purposeful behavior Memory, sequencing, making meaning of

language Speech organization and production Aspects of emotional response

Functions of the Temporal Lobe: Visual spatial recognition Attention Motivation Emotional modulation and interpretation Impulse and aggression control Interpretation and meaning of social contact Aspects of sexual action and meaning

Functions of Parietal Lobe: Sensory integration and spatial relations Bodily awareness Filtration of background stimuli Personality factors and symptom denial

Memory and nonverbal memory Concept formation

Functions of the Occipital Lobe: Vision Possible information holding area

Learning & Memory (thoughts): Thought processes involve patterns of stimuli

from many parts of the nervous system simultaneously.

Cerebral cortex Thalamus Limbic system Reticular formation

Memory traces New or reactivated pathways transmit

neural circuitsLimbic System:

Emotional behavior Includes several structures deep within the

brain Includes among others hippocampus &

amygdala Emotional behavior Emotional memoryHippocampus short term memory

hippocampal atrophy Alzheimer’s Amygdala modulation of social responses ie

fear, aggression, sexualOrigin of the Manifestations of Mental Illness:

Alterations in brain neuron functioning Destruction of those neurons Alterations in the neural connections among the

brain regionsSteps of Neurotransmission:

Synthesis of a transmitter substance Storage and release of the transmitter Binding of the transmitter to receptors on the

postsynaptic membrane Removal of the transmitter from the synaptic

cleftNeuromediators (neurotransmitters):

Acetylcholine Dopamine Norepinephrine & epinephrine Serotonin γ aminobutyric acid, glutamate, aspartate, and

glycine

Schizophrenia: Chronic, debilitating psychotic disorder that

involves the disconnection between thought and language

Affects the thinking, feeling, perceiving, behaving, and experiencing the environment

Onset between 17 and 25 years Men and women seem to be affected equally First degree relatives of a person with

schizophrenia have a 10 fold greater prevalence of the illness

Manifestations of Schizophrenia: Negative symptoms:

Reflect the absence of normal social and interpersonal behaviors

Absence of normal social and interpersonal behaviors

Alogia Avolition Apathy Affective flattening Anhedonia Blunted response to pain

Positive symptoms: Reflect the presence f abnormal

behaviors Incomprehensible speech Delusions Hallucinations Catatonic behavior Enhancement or a blunting of the senses Sensory overload due to loss of the

ability to screen external sensory stimuli

Disorders of Perception: Hallucinations:

Sensory perceptions that occur without external stimulation of the

relevant sensory organ Visual, auditory, tactile, olfactory Can occur with:

Epilepsy, tumors, metabolic, substance withdrawal, a variety of

psychiatric disorders Delusions:

Characterized by a false belief and the persistent, unshakable acceptance

of the false belief Types of delusions:

Persecution, influence, ill health, grandeur, poverty, possession

Major Groups of Antipsychotic Agents for Schizoprhenia:

Typical antipsychotics Include the phenothiazines (chlorpromazine), butyrophenones

(haloperidol), and thioxanthenes (chlorprothixene)

Atypical antipsychotics Exemplified first by clozapine, are more

effective in treating the negative symptoms of schizophrenia and produce fewer

extrapyramidal effectsDiagnosis of Schizophrenia:

Two or more of the following symptoms must be present for a significant portion of 1 month:

Delusions Hallucinations Disorganized speech Grossly disorganized or catatonic

behavior Negative symptoms

One or more areas of functioning must be significantly impaired and continuous signs of the disturbance must persist for at least 6 months

Goals of Treatment for Schizophrenia: Initially the goal may be primarily to reduce

agitation and the risk of physical harm Induce a remission Prevent a recurrence Restore behavioral, cognitive, and psychosocial

function to premorbid levelsNeuroimaging Studies:

Imaging studies do not generally diagnose mental illness, but do suggest a brain based problem

Mood Disorders: Depression: a mental state characterized by a

pessimistic sense of inadequacy and a despondent lack of activity

Mania: characterized by extremely elevated mood, energy, and unusual thought patterns

Affective disorders Affect approximately 21% of the

population Women affected twice as often as men 20–40% of adolescents who present

with major depression develop bipolar disorder within five years

Classification of Major Depression: Unipolar:

Characterized by a persistent unpleasant mood

Bipolar: Characterized by alternating periods of

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 episodesBipolar 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 5HTEffects 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 prolongedPTSD:

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

addictionBrain 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 impactDementia:

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 studiesDifferentiate 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 disorderAlzheimer’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, tertiaryHypopituitarism, hyperpituitarismGrowth hormone deficiencyHyper vs. hypothyroidismGraves disease: genetic, exopthalamusThyroid stormAdrenal Coritcal InsufficiencyCushing syndromeAddisons diseaseAdrenal hyperplasiaMalignant vs benign tumorsCommon cancers men vs womenIn situCachexiaNeoplasmS&S of urinary outflow obstruction & urine retentionStem cells unipotant, olgipotent, pluripotentCarcinogens, oncogenes, mutogenic, obstructionBladder distentionFrequencyOverflow incontinenceJaundiceBiopsyParaneoplasticViral carconogens vs oncogenic virusesManifestations of cancer cachexia, paraneoplastic

syndromes, tissue integrityGlioblastoma. Meningioma, sarcome, melamomaDifferentiate tumor makers from oncogenes &

carcinogens

Research Paper helphttps://www.homeworkping.com/