Chapter 4- Pathophysiology-Spring2024-UDST-Endocrine System-Winter2024 PDF

Introduction to Pathophysiology Dr Mouadh Abdelkarim Wilkins, Lippincott Williams &. Pathophysiology Made Incredibly Easy!  Chapter 04 Endocrine System Disorders Endocrine system disorders : 1- Insulin and Diabetes Mellitus 2- Parathyroid Hormone and Calcium Disorders 3- Pituit...

Introduction to Pathophysiology Dr Mouadh Abdelkarim Wilkins, Lippincott Williams &. Pathophysiology Made Incredibly Easy!  Chapter 04 Endocrine System Disorders Endocrine system disorders : 1- Insulin and Diabetes Mellitus 2- Parathyroid Hormone and Calcium Disorders 3- Pituitary Hormones Disorders 4- Thyroid Disorders 5- Adrenal Glands disorders Dr Mouadh Abdelkarim  Major Endocrine Glands  Hypothalamus  Pituitary gland  Pineal gland  Thyroid  Parathyroid glands  Thymus  Adrenal glands  Pancreas  Ovaries  Testes Location of Endocrine Glands Copyright © 2019 by Elsevier Inc. All rights reserved.  Endocrine System  Hormones as chemical messengers  Target receptors  Negative feedback systems  Chemical structure  Peptide  Steroid  Classification by Chemical Structure  Steroid  They are lipids and enter the cell nucleus to initiate transcription directly.  Nonsteroid  Needs a secondary messenger system to activate transcription in the nucleus Sources of Major Hormones and Their Primary Effects  Control of the Endocrine System  The endocrine and nervous systems regulate metabolic activities.  Negative feedback system  Positive feedback Blood clotting Child birth  Some hormones act as antagonists, such as  calcitonin and parathyroid hormone.  insulin and glucagon.  Endocrine Disorders  All disorders reflect impaired control or feedback.  Excess hormone levels  Tumor produces high levels  Excretion by liver or kidney is impaired.  Congenital condition produces excess hormone.  Endocrine Disorders (Cont.)  Deficit of hormone or reduced effects  Tumor produces too little hormone.  Inadequate tissue receptors present  Antagonistic hormone production is increased.  Malnutrition  Atrophy, surgical removal of gland  Congenital deficit  Diagnostic Tests  Blood tests  Check serum hormone levels  Radioimmunoassay  Immunochemical methods  Urine tests  Stimulation or suppression tests  Scanning, ultrasound, magnetic resonance imaging (MRI)  Biopsy  Treatment  Deficit may be treated with replacement therapy.  Excessive secretion may be treated with  medications.  surgery.  radiation. 1- Insulin and Diabetes Mellitus Dr Mouadh Abdelkarim  Diabetes mellitus—basic problem is inadequate insulin effects in receptor tissues  Deficit of insulin secretion  Production of insulin antagonists  Diabetes results in abnormal carbohydrate, protein, and fat metabolism.  Some tissues can transport glucose in the absence of insulin:  CNS, kidney, myocardium, gut, skeletal muscle Skeletal muscle can partially meet tissue needs without insulin.  Types of Diabetes  Type 1  Autoimmune destruction of beta cells in pancreas  Insulin replacement required  Acute onset in children and adolescents  Not linked to obesity  Genetic factors may play a role.  A- Type 1 Diabetes  Metabolic changes  Catabolism of fats and proteins Excessive amounts of fatty acids and metabolites Ketones in the blood Ketones, or ketone bodies, are acidic molecules made in your liver. When the liver breaks down cells, fat, or protein to give you energy, it makes ketones as by-products.   Ketonuria Decreased serum bicarbonate Decrease in pH of body fluids Ketoacids excreted in urine  Decompensated metabolic acidosis Low bicarbonate levels in the blood are a sign of metabolic acidosis. Dr Mouadh Abdelkarim  Types of Diabetes  Type 2  Noninsulin-dependent  Oral hypoglycemic medications may be used.  Caused by decreased production of insulin and/or increased resistance by body cells to insulin  Onset is slow and insidious, usually in those older than 50 years.  Associated with obesity  Component of metabolic syndrome  Increasing incidence in teens and young adults  B-Type 2 Diabetes  May be controlled by adjusting:  Dietary intake  Increase body’s use of glucose That is, with exercise  Reducing insulin resistance  Stimulating the beta cells of the pancreas to produce more insulin Control of Type 2 Diabetes (Cont.)  Monitoring blood glucose levels as ordered  Medication to stimulate the beta cells of the pancreas to produce more insulin  If insulin-dependent—proper administration of insulin to maintain glucose levels in normal range  Routine follow-up and blood testing  Initial Stage  Insulin deficit  Results in decreased transportation and use of glucose in many cells  Blood glucose levels rise (hyperglycemia)  Excess glucose found in urine  Large urine volume  Fluid loss through urine, resulting in dehydration  Dehydration causes thirst (polydipsia).  General Manifestations  Insulin deficit results in decreased transport and use of glucose in many cells.  Polyphagia  Fatigue  Blood glucose levels rise—hyperglycemia  Excess glucose in urine—glucosuria  Dehydration results from hyperosmolar filtrate.  Polyuria  Polydipsia  Diagnostic Tests  Fasting blood glucose level  Glucose tolerance test (OGTT)  Glycosylated hemoglobin test (HbA1c)  Clinical and subclinical diabetes  Monitor glucose levels over several months.  Treatment Principles  Maintenance of blood glucose levels in normal range  Helps reduce complications  Diet and exercise  Exercise reduces blood glucose level as skeletal muscle uses glucose.  Oral medication  Increase insulin secretion.  Reduce blood glucose levels.  Insulin replacement  Complications  Complications are directly related to duration and extent of abnormal blood glucose levels.  Many factors lead to fluctuations in serum glucose levels.  Variations in diet and alcohol use  Change in physical activity  Infection  Vomiting  Complications may be acute or chronic.  Acute Complications  Hypoglycemia (insulin shock)  More common with insulin replacement treatment  Can occur because of excess oral hypoglycemic drugs  Excess insulin in circulation Glucose deficit in blood Can be life-threatening or cause brain damage if untreated Often follows strenuous exercise Dosage error Vomiting Skipping meal after taking insulin Hypoglycemic Shock Copyright © 2019 by Elsevier Inc. All rights reserved.  Hypoglycemic Shock: Signs and Symptoms  Disorientation and change in behavior  Anxiety or decreased responsiveness  Decreased blood glucose level  Decreased BP, increased heart rate  Decreasing level of consciousness  Note: Immediate administration of glucose is required to prevent brain damage.  Emergency Treatment for Hypoglycemic Shock  If conscious, immediately give sweet fruit juice, honey, candy, or sugar.  If unconscious, give nothing by mouth. Intravenous glucose 50% is required.  Note: Diabetic ketoacidosis (diabetic coma or hyperglycemia, DKA) also causes loss of consciousness. The emergency treatment is insulin, fluid, and sodium bicarbonate.  C- Diabetic Ketoacidosis (DKA)  Occurs in insulin-dependent clients  More commonly seen in type 1 diabetes  Result of insufficient insulin in blood  High blood glucose levels  Mobilization and use of lipids to meet cellular needs result in production of ketoacids  May be initiated by infection or stress  May result from error in dosage, infection, change in diet, alcohol intake, or exercise Development of Diabetic Ketoacidosis Copyright © 2019 by Elsevier Inc. All rights reserved.  Signs and Symptoms  Thirst  Dry, rough oral mucosa  Warm, dry skin  Rapid pulse, but weak  Blood pressure is low as the vascular volume decreases.  Oliguria (decreased urine output) indicates that compensation mechanisms to conserve fluid in the body are taking place.  Ketoacidosis  Rapid, deep respirations (Kussmaul respirations)  Acetone breath (a sweet, fruity smell)  Lethargy and decreased responsiveness indicate depression of the central nervous system owing to acidosis and decreased blood flow. hyperpnea : abnormally rapid or deep breathing.  Metabolic Acidosis  Decreased serum bicarbonate levels and decreased serum pH  Dehydration progresses, renal compensation is reduced.  Serum pH falls.  Loss of consciousness  Electrolyte Imbalances  Primarily abdominal cramps  Nausea, and vomiting  Lethargy and weakness  Treatment  Insulin administration  Replacement of fluid and electrolytes  D- Hyperosmolar Hyperglycemic Nonketotic Coma (HHNK)  Occurs in type 2 diabetes  Insidious in onset and diagnosis may be missed  Often occurs in older clients and assumed to be cognitive impairment  Results in severe dehydration and electrolyte imbalances  HHNK Manifestations  Hyperglycemia  Severe dehydration  Increased hematocrit  Loss of turgor (dehydration)  Increased heart rate and respirations  Electrolyte imbalances result in  neurologic deficits.  muscle weakness.  difficulties with speech.  abnormal reflexes. Dr Mouadh Abdelkarim Chronic Complications of Diabetes Vascular problems  Increased incidence of atherosclerosis  Changes may occur in small and large arteries. 1- Microangiopathy—changes in microcirculation  Obstruction or rupture of small capillaries and arteries Tissue necrosis and loss of function Neuropathy and loss of sensation Retinopathy—leading cause of blindness Chronic renal failure—degeneration in glomeruli of kidney Vascular Problems with Diabetes Copyright © 2019 by Elsevier Inc. All rights reserved.  Chronic Complications of Diabetes (Cont.) 2- Macroangiopathy—affects large arteries  Result of abnormal lipid levels High incidence of heart attacks, strokes, peripheral vascular disease May result in ulcers on feet and legs—slow-healing Frequent infections and gangrenous ulcers Amputation may be necessary. 3- Peripheral neuropathy  Common complication caused by ischemia in microcirculation to peripheral nerves Impaired sensation, numbness, tingling, weakness, muscle wasting Diabetic Retinopathy Copyright © 2019 by Elsevier Inc. All rights reserved. Diabetic Nephrosclerosis Copyright © 2019 by Elsevier Inc. All rights reserved. Neuropathic Diabetic Foot Ulcer Copyright © 2019 by Elsevier Inc. All rights reserved.  Chronic Complications of Diabetes (Cont.)  Infections  Common and often more severe in diabetics  Infections in feet and legs caused by vascular and neurologic impairment  Fungal infections common Caused by Candida In vagina and/or oral cavity  Urinary tract infections  Dental caries  Gingivitis (gum inflammation) and periodontitis (serious gum infection)  Periodontal Disease in Diabetics Gingivitis is a common and mild form of gum disease (periodontal disease) Copyright © 2019 by Elsevier Inc. All rights reserved. Candidiasis Copyright © 2019 by Elsevier Inc. All rights reserved.  Chronic Complications of Diabetes (Cont.)  Cataracts  Opacity of lens in eye  Related to abnormal metabolism of glucose  Pregnancy  Complications in both mother and fetus may occur.  Increased incidence of spontaneous abortions  Infants born to diabetic mothers increased size and weight for date (fetal macrosomia). may experience hypoglycemia in first hours postnatally. Dr Mouadh Abdelkarim Potential Complications of Diabetes Mellitus 2- Parathyroid Hormone and Calcium Dr Mouadh Abdelkarim Parathyroid hormone : - 4 parathyroid glands - Release PTH in response to drop in serum calcium - Magnesium needed to activate PTH release - Effects on bone, Kidney and indirectly on intestines. Dr Mouadh Abdelkarim Dr Mouadh Abdelkarim  Action of PTH on bone  PTH causes resorption of bone. (osteoclastic activity).  This causes mobilization of Ca++ from the bone or demineralization.  Hence it increases serum Ca++ levels. Dr Mouadh Abdelkarim  Hypoparathyroidism  Leads to hypocalcemia Weak cardiac muscle contractions Increased excitability of nerves—spontaneous contractions of skeletal muscle  Causes Tumor Congenital lack of parathyroid Surgery or radiation in neck region Autoimmune disease Normal Control and Feedback of Calcium Dr Mouadh Abdelkarim Copyright © 2019 by Elsevier Inc. All rights reserved.  Parathyroid Hormone and Calcium (Cont.)  Hyperparathyroidism  Results in hypercalcemia Forceful cardiac contractions Osteoporosis Predisposition to kidney stones  Causes Tumor Secondary to renal failure Paraneoplastic syndrome (ectopic PTH production which increases bone resorption) Common Effects of Parathyroid Hormone Imbalance Copyright © 2019 by Elsevier Inc. All rights reserved. Dr Mouadh Abdelkarim 3- Pituitary Hormones Dr Mouadh Abdelkarim Dr Mouadh Abdelkarim  Pituitary Hormones  Adenomas are the most common cause of pituitary disorders.  Effect of mass  May cause pressure in the skull Headaches, seizures, drowsiness (sleepy), visual deficits  Effect on hormone secretion  Dependent on cells and location involved  May cause excessive or decreased release of hormones Growth Hormone (GH) Dr Mouadh Abdelkarim Control of Growth Hormone secretion Dr Mouadh Abdelkarim  Growth Hormone (GH)  Dwarfism  Deficit in growth hormone production and release  Gigantism (before puberty)  Excess GH prior to puberty and fusion of epiphysis  Acromegaly (after puberty)  Excess GH secretion in adults  Often associated with adenoma  Bones become broader and heavier.  Soft tissue grows. Enlarged hands and feet, change in facial features Giganitsm Acromegaly Dwarfism Dr Mouadh Abdelkarim Primary Gigantism Copyright © 2019 by Elsevier Inc. All rights reserved. Acromegaly Copyright © 2019 by Elsevier Inc. All rights reserved.  Pygmies of Africa>>>inability to synthesize significant amount of somatomedin C despite GH [] NORMAL Lorain-Levi dwarfism (mutations in the gene for the GH receptor.) Dr Mouadh Abdelkarim Antidiuretic Hormone (ADH) Dr Mouadh Abdelkarim Dr Mouadh Abdelkarim  Antidiuretic Hormone (ADH)  Diabetes insipidus—deficit of ADH  Adenoma  May originate in the neurohypophysis Head injury or surgery Possible genetic problem Replacement treatment required Diabetes insipidus is a rare condition that causes your body to make a lot of urine that is "insipid," or colorless and odorless.  Inappropriate ADH syndrome (SIADH)  Excess ADH May be temporary, triggered by stress; may be secreted by an ectopic source, such as a tumor  Treatment Diuretics Sodium supplements Dr Mouadh Abdelkarim 4- Thyroid Disorders Dr Mouadh Abdelkarim  - Two thyroid hormones - T4 – thyroxine (90%) - T3 – triiodothyronine (10%) - Released in response to TSH - Disorders may result from pituitary or thyroid gland dysfunction - Hyperthyroidism (Graves Disease) - Hypothyroidism Hypothalamus-Pituitary-Thyroid Gland Feedback Copyright © 2019 by Elsevier Inc. All rights reserved.  Goiter A goiter is used to describe any enlarged thyroid gland. The thyroid is a butterfly-shaped gland located in your neck.  Endemic goiter (iodine deficiency)  Hypothyroid condition in regions with low iodine levels in soil and food  Goitrogens  Foods that contain elements to block synthesis of triiodothyronine (T3) and thyroxine (T4)  Toxic goiter  Results from hyperactivity of thyroid gland  Iodine Is Required for Formation of Thyroxine : To form normal quantities of thyroxine, about 50 milligrams of ingested iodine in the form of iodides are required each year, or about 1 mg/week. To prevent iodine deficiency, common table salt is iodized with about 1 part sodium iodide to every 100,000 parts sodium chloride. Dr Mouadh Abdelkarim  Hyperthyroidism  Related to autoimmune factor  Hypermetabolism and increased stimulation of SNS  Increased body temperature  Sweating  Soft silky hair and skin  Reduced BMI  Insomnia  Hyperactivity  Hyperthyroidism (Cont.)  Toxic goiter  Exophthalamos  Presence of protruding, staring eyes, decreased blink and eye movement  Result of increased tissue mass in the orbit  May result in visual impairment Exophthalmos Copyright © 2019 by Elsevier Inc. All rights reserved.  Hypothyroidism  Iodine deficit  Hashimoto thyroiditis  Autoimmune disorder  Tumor  Surgical removal or treatment of gland  Cretinism  Results in short stature and severe cognitive deficits  Untreated congenital hypothyroidism  May be related to iodine deficiency during pregnancy Hashimoto’s Disease Most common cause of hypothyroidism Autoimmune lymphocytic thyroiditis Antithyroid antibodies: Females > Males Runs in Families! Dr Mouadh Abdelkarim  Hypothyroidism Manifestations  Goiter if cause is endemic iodine deficiency  Intolerance to cold  Increased BMI  Lethargy and fatigue  Decreased appetite  Myxedema in severe, untreated hypothyroidism Comparison of Hypothyroidism and Hyperthyroidism Copyright © 2019 by Elsevier Inc. All rights reserved. 5- Adrenal Glands Cortex Medulla Dr Mouadh Abdelkarim  Adrenal Glands  Adrenal medulla  Pheochromocytoma (is a type of neuroendocrine tumor that grows from cells called chromaffin cells)  Adrenal cortex  Cushing syndrome  Addison disease  A- Adrenal Medulla  Pheochromocytoma  Benign tumor of the adrenal medulla—secretes epinephrine, norepinephrine, and possibly other substances  Occasionally, multiple tumors  Headache, heart palpations, sweating, intermittent or constant anxiety  B- Adrenal Cortex  B-1- Cushing syndrome  Caused by an excessive level of glucocorticoids; possible result of: Adrenal adenoma Pituitary adenoma Ectopic carcinoma Iatrogenic conditions Substance abuse Dr Mouadh Abdelkarim  Cushing’s syndrome results from continued high levels of glucocorticoids.  Causes:  pituitary adenoma 75-90%  adrenal adenoma, carcinoma  over-secretion of ACTH  high pharmacological doses of exogenous glucocorticoids  Characterized by changes in carbohydrates and protein metabolism, hyperglycemia, hypertension, and muscle weakness. Dr Mouadh Abdelkarim  Cushing Syndrome  Changes associated with Cushing syndrome  Change in person’s appearance Round face, with ruddy color Truncal obesity, with fat pad between scapulae Thin limbs Thin hair Fragile skin, striae  Cushing’s Syndrome Signs:  Fat is deposited in the body trunk (central obesity)  Buffalo hump  Moon face (subcutaneus fat in cheeks and submandibular)  Purple (red) striae  Blood-glucose levels rises chronically, causing adrenal diabetes Dr Mouadh Abdelkarim Cushing Syndrome (Cont.) Copyright © 2019 by Elsevier Inc. All rights reserved.  B-2-Addison Disease  Deficiency of adrenocorticoid secretions  Autoimmune reaction is a common cause.  Adrenal gland may be destroyed by hemorrhage or infection. Manifestations  Decreased blood glucose levels  Inadequate stress response  Fatigue  Weight loss, frequent infections  Low serum sodium concentration  Decreased blood volume  Hypotension  High potassium levels Comparison of Addison Disease with Cushing Syndrome Copyright © 2019 by Elsevier Inc. All rights reserved. A patient comes to the clinic with a moon face, excess adipose tissue, and acne. Which of the following diagnoses should the patient be tested for? 1.Cushing's syndrome 2.Addison's disease 3.Diabetes 4.Hyperthyroidism Dr Mouadh Abdelkarim A patient with larger than normal hands and feet is symptomatic for which of the following endocrine disorders? 1.Cushing's syndrome 2.Grave's disease 3.Hypermegaly 4.Acromegaly Dr Mouadh Abdelkarim  A patient presents with polyuria and thirst. There appears to be no elevation of glucose in the body, however, the serum osmolality appears to be low. Upon performing the water deprivation test, the osmolatity is still low. Which of the following is true? A. The problem is in the pituitary B. The problem is in the kidneys C. The patient has diabetes mellitus D. The patient has high ADH in the serum E. B and D Dr Mouadh Abdelkarim