Module 3: Endocrine System Disorders & Nervous System Disorders Flashcards
Discuss the etiology of endocrine disorders in general.
Disorders occur because of hyposecretion, hypersecretion, or nonresponsiveness by target cells.
Etiology may be congenital, infectious, autoimmune, neoplastic, idiopathic, or iatrogenic.
Causes of hypersecretion
secreting tumors, autoimmune disease, or excessive stimulation of the gland by trophic signals.
Causes of hyopsecretion
failure or congenital absence of glandular tissue, autoimmune destruction, surgical removal of the gland, or lack of normal trophic signals.
Hyporesponsiveness
Clinically similar to hyposecretion; due to target tissue dysfunction - also called tissue resistance.
Functional disorders
Caused by non-endocrine disease such as chronic renal failure, liver disease, or heart failure
Tissue resistance
Occurs when target tissue fails to respond to a hormone (hormone resistance or target tissue resistance)
Iatrogenic
Induced by medical treatments such as chemotherapy, radiation therapy, or surgical removal of glands
Treatment for endocrine hyperfunction involves removal or destruction of glandular tissue with resultant chronic hypofunction
Chronic hormone replacement therapy may be required
Classification of Endocrine Disorders
Primary: intrinsic malfunction of the hormone-producing gland
Secondary: abnormal pituitary secretion of trophic signals
Since clinical manifestations are similar, lab results can help distinguish between primary and secondary
Explain the feedback-loop systems in thyroid disorders and how laboratory testing is based on feedback loop communications.
There is a feedback loop communication between the hypothalmic-pituitary system and the target gland.
Ex. In primary hypothyroidism, the thyroid fails to secrete thyroid hormones and serum T4 (thyroxine) drops. TSH levels rise as the pituitary gland attempts to stimulate the malfunctioning thyroid.
In secondary hypothyroidism, the pituitary gland fails to release TSH, secondarily reducing thyroid gland production, so both T4 and TSH are low.
Hypothyroidism Etiology and Pathogenesis
primary & secondary
Deficient Thyroid hormone
Primary (majority are primary due to intrinsic dysfunction)
Congenital, defective hormone synthesis, iodine deficiency, anti-thyroid drugs, iatrogenic loss of thyroid tissue
Secondary – related to pituitary or hypothalamic failure – cause pituitary tumor or treatment of tumor
Clinical manifestations of primary hypothyroidism (which includes acute and subacute thyroiditis, painless thyroiditis, pp thyroiditis, autoimmune thyroiditis, iodine deficiency, iatrogenic)
.
(lab results and general symptoms)
Low T4 and high TSH Lethargy Weakness Dry, pale, cool, coarse skin Cold Intolerance Weight gain Constipation Bradycardia, wide pulse pressure Dyspnea, chest pain Possible goiter Coarse hair Sluggish reflexes, mental impairment, forgetful, depressed affect, deafness Facial edema (esp. periorbital) Heavy, prolonged menses, infertility, decreased libido
Clinical manifestation in an infant.
Few sx present at birth. Usually become sx in the first few months of life: dull appearance, thick protuberant tongue, thick lips (poor feeding), prolonged neonatal jaundice, poor muscle tone, bradycardia, mottled extremities, umbilical hernia, and hoarse cry.
Hashimoto’s disease
1) Most common cause of acquired thyroiditis
2) AKA autoimmune thyroiditis – will cause destruction of thyroid tissue by circulating auto-antibodies and infiltration by lymphocytes
3) Postpartum thyroiditis – like Hashimoto’s – occurs 6-8 months pp – spontaneous recovery in 95% of cases
Clinical manifestations in older children
Growth retardation, delayed bone development and delayed or precocious puberty may occur in addition to the symptoms displayed by adults.
Define Myxedema
Generalized non-pitting edema which occurs in severe or prolonged thyroid deficiency.
Etiology and pathogenesis of Hyperthyroidism
1) Excessive thyroid hormone synthesis & secretion
2) Grave’s disease – most common cause – result of stimulation of thyroid with antibodies against TSH receptor (Type II). Target is not destroyed but malfunctions.
3) Auto-antibodies bind with receptors for TSH and stimulate production of T4
- Feedback loop out of commission
Clinical manifestations of hyperthyroidism (Graves)
1) Adrenergic stimulation – tachycardia, nervousness, lid lag, tremor, increased B/P
2) Excess T4 – increased O2 consumption, changes in protein metabolism
3) Immunologic stimulation – goiter
4) Triad = hyperthroidism, exophthalmus, goiter
5) Thyroid Storm
General symptoms: sleeplessness, nervousness muscle weakness susceptible to infection skin: warm, silky, damp heat intolerance Increased appetite with wt. loss increased gastric motility tachycardia dyspnea diffuse or nodular enlarged thyroid silky hair, loose nails hyperreflexia eyes: burning, tearing, diplopia, lid lag, prominent (exophthalmia with Graves) absence of forehead wrinkling decreased or absent menses
Explain stress hyperglycemia.
Hormones released during stress increase blood glucose levels and oppose the effects of insulin. Stress hyperglycemia can be precipitated by catecholamines, glucocorticoids, and glucagon.
Modifiable risk factors for diabetes
Type 2 - Obesity, sedentary lifestyle
Non-modifiable risk factors for diabetes
Type 1 - genetic, viral infection or environmental exposure triggers autoimmune response, idiopathic
Type 2- family history, member ethnic minority, female, most are over age 40
Type 1 Diabetes definition.
Characterized by destruction of the B cells of the pancreas. Peak ages: 2, 4-6, 10-14, but can occur at any age. More prevalent in caucasians and males.
Type 1 Diabetes etiology.
1A is immune mediated (most common of type 1). 80-90% are polygenic. Monogenic is rare.
- Result of autoimmune attack on B cells of pancreas. Can be triggered by virus or environmental exposure.
- Strongly associated with presence of a gene in the major histocompatibility complex on chromosome 6 & HLA associated.
1B etiology is not known - idiopathic B-cell destruction without autoimmune markers or HLA association.
Diabetes Type 1 Pathogenesis
1) Autoantigens form on insulin producing beta cells and begin circulating.
2) Processing and presentation of autoantigen occurs by APC’s (antigen presenting cells).
3) T helper 1 & 2 lymphocytes are activated.
4a) T helper 1 activates macrophages with release of Interleuken 1 and tumor necrosis factor alpha. Also activates autoantigen specific T cytotoxic (CD8) cells.
4b) T helper 2 cells activate B lymphocytes to produce islet cell autoantibodies and antiGAD65 antibodies.
5) These cause destruction of beta cells with decreased insulin secretion.
Type 1 Diabetes clinical manifestations.
Hyperglycemia
Polydipsia – fluid loss increases thirst
Polyuria- increased serum glucose causes osmotic diuresis
Polyphagia – starved cells trigger neural response to eat more
Weight loss – fat is being burned for energy
Fatigue
Type 2 Diabetes etiology.
1) Resistant to the action of insulin on peripheral tissues.
2) More common and continues to rise in incidence
3) Native Americans (Pima Indians, esp.), Hispanics, Blacks
4) Mostly >40 years old but may be seen in adolescents
Type 2 Diabetes pathogenesis
1) Genes influence insulin resistance (60-80% of cases) or beta cell dysfunction OR both
2) May also see abnormal glucagon secretion
3) Beta cell function is affected due to amyloid deposits, fatty deposits in pancreas and liver, or pancreatic fibrosis or cytokine toxicity but insulin is still produced for a time
* Insulin resistance and b-cell dysfunction produce a relative lack of insulin. Pancreas produces sufficient insulin, but it is resistant to effective use resulting in increased blood glucose levels.
Define GDM
Glucose intolerance of variable severity with onset or first recognition during pregnancy.
GDM etiology
1) Normal pregnancy is a diabetogenic state
2) Resembles type 2 - tissue insulin resistance (most likely precipitated by placental hormones)
3) Wt. gain in pregnancy also increases insulin resistance
Risk factors for GDM
Risk factors: family history, ethnic group, >25 years old, prior history of GDM or PCOS, overweight, OB complication, large baby
Complications of GDM
Complications- macrosomia, newborn hypoglycemia
MODY - mature-onset diabetes of the young
Subset of Type 2. There are 6 types of MODY Genetic - Autosomal Dominant gene Clinical Manifestations (Type 2) Normal weight, hyperlipidemia, non-specific pruritis, recurrent infection, visual changes, parathesias, non-ketotic, responds to oral meds.
LADA
1) Latent autoimmune diabetes in adults.
2) Usually over age 35
3) Characteristics suggestive of type 2, but have b-cell antibodies and quickly become insulin dependent.
Microvascular complications in diabetes
Thickening of the capillary basement membrane, endothelial hyperplasia, thrombosis, and pericyte degeneration are characteristic
- Visual changes, retinopathy - Nephropathy - neuropathy
Macrovascular complications in diabetes
Prevalent in Type 2
Atherosclerotic disease unrelated to severity of DM
-Coronary artery disease – MI and CHF
-Stroke
-Peripheral Vascular Disease (AKA peripheral artery disease)
*damage to the large blood vessels providing circulation to the brain, heart, and extremities
Diabetic neuropathy
1) Autonomic dysfunction - gi disturbances, bladder dysfunction, tachycardia, postural hypotension and sexual dysfunction
2) Sensory dysfunction - carpal tunnel, parasthesias or lack of sensation in feet and lower legs
Geriatrics and diabetes
1) DM Type II is more prevalent among persons over age 60 – about 60% of diabetics are older than 60
2) Increased body fat, decreased activity contribute to insulin resistance
3) Insulin secretion decreases with age
4) More difficult to diagnose DM II in older person
Diagnostic labs for diabetes
Pre diabetes: 100-125 fasting
140-199 2hr (75gm OGTT)
5.7-6.4 HbA1C
Diabetes: >126 fasting OR
>200 casual with symptoms (polyuria, polydipsia, & unexplained wt loss OR
>200 2hr (75gm OGTT) OR
>6.5 HbA1C
Define obesity
Excessive accumulation of adipose tissue; BMI 30 or higher
Obesity etiology
Etiology – lifestyle choices, environment, genetics, epigenetics – mostly excess intake of calories
Complications of obesity
Inflammation and contribution to chronic disease
Metabolic Syndrome characteristics
Abdominal adiposity Increased free fatty acid Insulin resistance Low serum HDL Hypertriglyceridemia Hypertension
Hormones involved in the development of Metabolic Syndrome
Resistin (Jamaluddin, Weakley, Yao, Chen, 2012)
Leptin
Ghrelin
Apelin
Health consequences related to metabolic syndrome
“deadly cocktail”
May precede dx of diabetes and cardiac disease
Metabolic function and age
Alteration in molecular makeup of insulin
Higher levels of serum proinsulin
Age alters insulin receptors
Body fat increases causing changes in lipid metabolism
Metabolic rate slows with age
Muscle mass and growth hormone decrease (somatopause)
Define stroke
sudden onset of neurologic dysfunction due to cardiovascular disease that results in an area of brain infarction
Risk factors for stroke.
Specific one for emobolic stroke.
**Females affected more frequently
Hypertension, diabetes, hyperlipidemia, cigarette smoking, advancing age, family hx, and previous stroke.
**Embolic stroke - cardiac disease complicated by atrial fib
Define ischemic stroke and list the different types.
Result from sudden occlusion of a cerebral artery secondary to thrombus formation or embolization.
- Thrombotic
- Embolic
- TIA
- Lacunar
Thrombotic stroke risk and details.
1) Associated with atherosclerosis and hypercoagulable states.
2) Risk reduction: reduce atherosclerosis & platelet aggregation
3) Atherosclerotic plaques in the carotid arteries may be evident as carotid bruits.
Embolic stroke risk and details.
1) Emboli are usually from a cardiac source, but carotid artery plaques can lead to downstream embolization.
2) Atrial fib allows stagnation of blood in the left atriium, which increases risk of emboli.
How quickly does damage occur in stroke and in what time frame should treatment begin?
Neurologic deficits become evident after 1min of insufficient O2. Treatment to salvage the penumbra should begin within 3 hous.
Define Lacunar stroke & list risk factors.
1) <1cm area in the small arteries of the basal ganglia
2) Smoking & hypertension
Define TIA and associated risk.
Transient Ischemic Attack - Neurologic symptoms completely resolve within 24hours.
- 80% recur and can progress to stroke
Clinical manifestations of ischemic stroke
contralateral hemiplegia, hemisensory loss, and contralateral visual field blindness
Define Hemorrhagic stroke, where does it most often occur, mortality
Hemorrhage within the brain parenchyma; most often occurs in the basal ganglia or thalamus; Morbidity and mortality is significantly higher than with ischemic stroke.
38% mortality-usually within minutes to hours.
Clinical manifestations of hemorrhagic stroke
1) Can significantly increase ICP - may lead to herniation and death
Define meningitis and name most common organism.
Infection that causes inflammatory reaction in the meninges, the CSF and ventricles
Most common: Streptococcus pneumoniae
Etiology of meningitis
Organisms may gain access to the CNS through the bloodstream, direct extension from a primary site or along peripheral and cranial nerves, or through maternal-fetal exchange
Risk factors for meningitis.
immunocompromise, debilitation, poor nutrition, radiation, steroid therapy, contact with vectors
Clinical manifestations of meningitis.
Classic presentations: headache, fever, stiff neck (meningismus), and signs of cerebral dysfunction (confusion, delirium)
- Kernig Sign: unable to straighten leg with hip flexed to 90 degrees - Brudzinski Sign: bringing head toward chest causes flexing of hips and knees as well as pain
Define encephalitis and list cause.
An inflammation of the brain most often caused by virus. HSV 1 is most common. West Nile Virus-transmitted by mosquitoes.
Clinical manifestations of encephalitis.
Manifestations-Typical presentation of West Nile includes fever, HA, malaise, muscle pain, confusion, unconsciousness, seizures, increased intracranial pressure
Define seizure.
What makes it epilepsy / seizure disorder?
1) A transient neurologic event of paroxysmal abnormal or excessive cortical electrical discharges manifested by disturbances of skeletal motor function, sensation, autonomic visceral function, behavior, or consciousness.
2) Epilepsy / SD - recurrent
Etiology of seizures.
Causes: cerebral injury, lesions, metabolic/nutritional disorders, idiopathic
Pathogenesis of seizures.
May be triggered by specific stimuli such as flashing lights, fever, loud noises
- Due to an alteration in membrane potential that makes certain neurons abnormally hyperactive and hypersensitive to changes in their environment (epileptogenic focus)
- Nearby and distant neurons can be recruited into the seizure
- Aura/prodrome: subjective sense of an impending seizure
Define Generalized Seizures.
Generalized: whole brain surface is affected during the seizure
Involvement of thalamus and RAS system results in loss of consciousness
List types of generalized seizures.
- Absence (petite mal): occurs in children, staring spells that last only seconds
- Atypical absence: myoclonic jerks, automatisms with the staring spell
- Myoclonic: single/several jerks
- Atonic (drop attack): fall down
- Tonic-clonic (grand mal): jerking of many muscles
Define status epilepticus
Status epilepticus: continuing series of seizures without a period of recovery between episodes; can be life-threatening
- can occur in all seizure types, but most concerning with tonic-clonic
Define Partial Seizures
Partial seizures: abnormal electrical activity restricted to one brain hemisphere
List types of Partial seizures.
1) Simple
- No change in level of consciousness; motor, sensory, and/or autonomic symptoms common
2) Complex: change in consciousness
3) Partial with secondary generalization
- Starts as simple but advances to generalized
Facts about Alzheimers
- Most common cause of dementia (60-80% of dementias)
- 1 in 8 >65; almost 50% >85
- Irreversable, steady memory loss and eventual complete incapacitation due to degeneration of neurons, brain trophy, amyloid deposits & neruofibrillary tangles.
- Diagnosis based on elimination of other causes
Causes of vascular dementia.
*Results from single cerebrovascular insults (cerebral infarction), multiple lacunar infarcts, or microvasscular pathology.
Risk factors and clinical manifestations of vascular dementia.
Risk factors: stroke, hypertension, and diabetes
Clinical manifestations:
Early: memory loss, especially short-term memory, long-term memory may be preserved; thinking ability declines, decreasing ability to function at work and in social settings; anxiety, agitation
Multiple Sclerosis facts.
Destruction of CNS myelin, sparing peripheral nervous system
Affects females more than males
Affects Whites more than any other race
Autoimmune process
Stages –early, remission, exacerbation, late degeneration – permanent disability
**Not a linear disease
Bell’s Palsy facts.
Idiopathic neuropathy of the facial nerve (CN VII); paralysis of the muscles on one side of the face
Etiology: viral
3 times more frequent in pregnancy due to edema; 3rd trimester or first 2 weeks pp; has been associted with preeclampsia. Full recovery expected but may take months pp.
