NURS 241 Exam 3 Endocrine 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 receptors Control 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
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
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
• 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
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
– 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
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
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:
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:
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
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
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
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
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