Endocrine and Hepatobiliary Flashcards
_____ system
• Maintain metabolic equilibrium (homeostasis)
• Secrete chemical messengers (hormones)
• Regulate activity of various organs
• Process of feedback inhibition
• Increased activity of target tissue, typically down-
regulates activity of gland secreting stimulating
hormone
•diseases
a. diseases of under/over-production of hormones
b. diseases associated with development of mass
lesions
Endocrine System
• Base of brain-sella turcica • Connected to hypothalamus a. stalk composed of axons b. venous plexus • Central role in regulation of other endocrine glands • Two components a. anterior lobe (adenohypophysis) b. posterior lobe (neurohypophysis) • Diseases divided according to lobe mainly affected
Pituitary gland
• Produces growth hormone
• Somatotrophs
• Produces prolactin
• Lactotrophs
• Produces adrenocorticotrophic hormone
• Corticotrophs
• Produces thyroid simulating hormone
• Thyrotrophs
• Produces follicle stimulating hormone and luteinizing
hormone
• Gonadotrophs
- Pituitary Adenomas
- Radiation Treatment
- Neurosurgery
- Sheehan Syndrome
- Ischemic necrosis of pituitary gland
- Pituitary Dwarfism
- Amenorrhea & Infertility
- Libido & Impotence
- Postpartum lactation failure
- Hypothyroidism
- Hypoadrenalism
Hypopituitarism
- Pituitary Adenomas
- Pituitary Hyperplasia
- Pituitary Carcinomas
- Hypothalamic disorders
- Gigantism
- Acromegaly
- Cushing disease
Hyperpituitarism
• Primary tumor • Excess growth hormone (GH) • Adenoma of anterior pituitary • 2nd most common • Affects all “growing tissues” • Gigantism- before growth plate closure
Hyperpituitarism
•Generalized overgrowth• 3 standard deviations •Headaches •Chronic fatigue •Arthritis, osteoporosis • Muscle weakness •Hypertension •Congestive heart
Gigantism
• Late diagnosis • Poor vision; photophobia • Enlarged skull, hands, feet, ribs • Soft tissue, viscera • Enlarged maxilla, mandible, nasal and frontal bones, maxillary sinus • Intraoral: • Diastemas • Malocclusion • Macroglossia • Enlarged lips • Sleep apnea
Acromegaly
\_\_\_\_\_\_\_ pituitary issues: • Diabetes Insipidus (Central) • Polyuria • Dilute urine • Polydipsia • Secretions of Inappropriately High Levels of ADH (SIADH) • Hyponatremia • Cerebral edema • Neurologic dysfuction • Total Body Water • Blood volume normal • No peripheral edema
Posterior pituitary
____ controls TSH secretion
TRH
_____ controls T3 and T4 production
TSH
What 3 things are responsible for thyroid function? (glands)
Hypothalamus
Pituitary
Thyroid
What 3 things are responsible for thyroid function? (glands)
Hypothatlamus
Pituitary
Thryoid
\_\_\_\_\_ hypothyroidism • Intrinsic abnormality in the thyroid • Surgery • Radiotherapy • Autoimmune
Primary
_____ hypothyroidism
• Pituitary failure
Secondary
- Adult
- Generalized fatigue
- Apathy
- Mental sluggishness
- Listless
- Cold intolerance
- Overweight
Myxedema
• Childhood • Impaired skeletal development • Severe mental retardation • Short stature • Course facial features • Delayed tooth eruption
Cretinism
Symptoms of ______:
- Cold intolerance
- Fatigue, lethargy
- Weight gain
- Constipation
- Bradycardia
Hypothyroidism
• Autoimmune • Painless enlargement • Symmetric & diffuse • Risk of B-cell non- Hodgkins Lymphomas
Hashimoto thyroiditis
Clinical signs and symptoms Goiter (small) Exophtalmus (frequent) Heat intolerance Weight loss Malabsorption and diarrhea Tachycardia Irritability and anxiety Most common causes Autoimmune - Graves’ disease and Hashimoto’s thyroiditis Laboratory T4 and Free T4 elevated T3 and Free T3 elevated TSH and TRH suppressed
Hyperthyroidism
Symptoms of _____:
- Weight loss
- Nervousness
- Rapid pulse
- Goiter
- Muscle wasting
Hyperthyroidism
- Tachycardia
- Increased appetite
- Weight loss
- Exophthalmos
- Intolerance to heat
Graves disease
• Diagnosis • TSH • Primary-low • Secondary- normal to high • T4 (T3) increased • Treatment • Ablation • Significance • Thyroid storm • Caused by infection, stress, trauma • Elevated body temp. • Tachycardia • 20-40% mortality
Graves disease
• Thyroid enlargement • Impaired synthesis of thyroid hormone • Iodine deficiency • Endemic • Hyperplasia of follicles • Pituitary stimulation • Maintenance of minimal function (euthyroid) • Diffuse early on, then nodular • Diet deficient in iodine • Decreased output of T3 & T4 by thyroid • Pituitary responds by secreting TSH • Thyroid hyperplasia
Goiter
Derived from developing pharyngeal pouches
Lie in close proximity to upper and lower poles of each thyroid
lobe
May be found on path of descent of pharyngeal pouches –
carotid sheath, thymus, anterior mediastinum
Secrete Parathormone (PTH) which, with calcitonin regulates
calcium homeostasis –controlled by the level of free (ionized)
calcium
Parathyroid gland
_____: Activates osteoclasts activity
Increases Ca renal tubular resorption
Increases conversion of Vit. D into the active
dihydroxy form in the kidneys
Increases urinary excretion of phosphates
Increases Ca absorption by the GI tract.
PTH:
- Hypocalcemia
- Tetany
- Chvostek Sign
- Tapping CN VII
- Muscle contraction
- Eye, mouth, nose
- Trosseau sign
- Occluding circulation of forearm
- Carpal spasm
Hypoparathyroidism
_____ hyperparathyroidism
Adenoma
Hyperplasia
Carcinoma
Morphologic changes
Skeletal changes - bone resorption
- Formation of bone cysts and hemorrhages
(osteitis fibroso –cystica)
- Brown tumors
-Urinary tract stones (nephrolithiasis)
- Metastatic calcification
Serum calcium levels, especially Ionized calcium levels are high
•Hypercalcemia
• Hypophosphatemia
• Increased urinary excretion of both calcium and
phosphate
Primary
______ hyperparathyroidism:
Calcium is chronically depressed and low serum calcium
levels lead to compensatory hyperactivity of the
parathyroids
Serum phosphate levels are elevated
Causes
Chronic renal failure
Vitamin D deficiency
Inadequate dietary calcium
Steatorrhea
Morphology
Hyperplastic parathyroid glands
Bone chages (see primary hyperparathyroidism)
Metastatic calcification
Not as severe as in primary hyperparathyroidism
Related to symptoms secondary to chronic renal failure
Bone abnormalities (renal osteodystrophy)
Calciphylaxis
Tertiary hyperparathyroidism
Secondary
- Osteomalacia & loss of lamina dura
- Brown tumor
- Nephrolithiasis
- Peptic/duodenal ulcers
- Mental changes
Hyperparathyroidism
• Increases serum calcium
• Activates osteoclasts
• Increases renal tubular reabsorption of
calcium
• Increases renal conversion of Vit D
• Increases urinary excretion of phosphate
• Increased gastric absorption of calcium
PTH
_____ portion of adrenal gland:
• Aldosterone
• Regulated by angiotensin II
• Zona Glomerulosa
_____ portion of adrenal gland:
• Glucocorticoids (cortisol)
• Regulated by ACTH (biofeedback)
• Zona Fasiculata
_____ portion of adrenal gland:
• Androgens
• No feedback with ACTH
• Zona Reticularis
- Destruction of adrenal cortex
- Production of adrenal corticosteroid hormones
- Autoimmune
- Metastatic carcinoma
- Infections
- TB
- Deep fungal
- Secondary hypoadrenocorticism
- Disorder of hypothalamus or pituitary gland
Addison’s disease
- Clinical symptoms appear late
- Weakness & Fatigue
- Hypotension (postural)
- GI disturbances
- Nausea/ Vomiting (N/V)
- Anorexia
- Diarrhea
- Weight Loss
- Salt cravings ( K+ ↑, Na+↓,)
- Hyper-pigmentation (Bronzing)
- ACTH precursor stimulates melanocytes
- Frictional areas
- Adrenal Crisis (Acute)
- Abdominal pain
- Hypotension
- Vascular collapse
Addison’s disease
\_\_\_\_\_\_ Hypercortisolism: • Too much endogenous steroid • Females 5x • 3rd decade • Pituitary adenomas (ACTH) • 50% • Cushing disease • Adrenal hyper/neoplasia • 10-20% • Neuroendocrine tumors • Produce ACTH • Small Cell Lung Carcinoma
•Primary hypercortisolism
______ Hypercortisolism:
• Most common • Exogenous • Rule of 2s • Can become hypocortisol without taper
•Secondary hypercortisolism
- Presentation
- Central obesity
- Peripheral wasting
- Buffalo hump
- “Moon facies”
- Abdominal striae
- Hirsutism
- Poor wound healing
- Diabetes
- Hyperglycemia
- Osteoporosis
- Hypertension
Cushing syndrome
• AD • Marfanoid body type • Medullary thyroid carcinoma • Pheochromocytomas • Adrenal medulla • Neuromas • Can be first sign • Soft painless papules • Lips, conjunctiva, tongue, palate, buccal mucosa • Sentinel neuromas
MEN 2B
\_\_\_\_\_ Pancreas • Secretes enzymes • Digestion • Inactive proenzymes • Acute pancreatitis • Chronic pancreatitis • Cancer
• Exocrine pancreas
\_\_\_\_\_\_ Pancreas • Secretes hormones • Glucose homeostasis • Other metabolic activities • Diabetes mellitus • Beta cells in the islets of Langerhans
• Endocrine pancreas
• Injury to acinar cells • Interstitial or edematous pancreatitis • Mild • Reversible • Acute hemorrhagic pancreatitis • Alcoholism • Chronic biliary disease Etiology: • Metabolic • Alcoholism • Hyperlipoproteineimia • Hypercalcemia • Drugs • Thiazide diuretics • Genetic
Acute Pancreatitis
- Destruction of pancreatic parenchyma
- Intermittent “acute” attacks
- Alcoholism
- Obstruction of pancreatic duct
- Mechanical blockage
- Congenital defects
- Cancer
- Inspissated mucous
- Chronic injury to acinar cells
Chronic pancreatitis
• Hyperglycemia
• Lack of insulin (Type 1)
• Resistance to insulin (Type 2)
• Combination
• 21 million people ( 7% of population)
• Loss of insulin (anabolic) results in a catabolic state
affecting glucose, fat & protein metabolism
Diabetes mellitus
• Archaic terminology: Insulin Dependent DM, juvenile-onset DM • Autoimmune destruction of B cells in the Islets of Langerhans (insulitis) • Absolute deficiency • Destruction of Beta cells • Only 10% diabetics • Avg. age of onset- 14 yo • Emergencies • Acute: hypoglycemia • Chronic: ketoacidosis 180 •Cause• Destruction of β-cells • Autoimmune • T cell mediated • Auto-antibodies • Genetic • 30-70% twin concordance • HLA-DR3, DR4 (90-95%) • Environmental? • Infectious •Diagnosis ( DM1 or 2) • WNL= 70-120 mg/dL • Any of these • ≥ 200 mg/dL + S/S • Fasting ≥ 126 mg/dL • OGTT ≥ 200 mg/dl (2 hrs)
T1Dm
• Adult onset
• “Relative” lack of insulin
• 80-90% of diabetics
• Insulin resistance
• Early Normal blood insulin level
• Target tissue Resistance
• β-cell dysfunction fails to
compensate
• Demographics are changing
• Ketoacidosis (rare)
• Coma due to hyperosmolarity
• Archaic terminology: Non-Insulin dependent DM, adult/maturity-onset DM
• Inadequate secretion of insulin from the pancreas
• Reduced tissue sensitivity to insulin (liver, skeletal muscle, adipose tissue)
• Initially, hyperinsulinemia may compensate for peripheral insulin resistance
and normal plasma glucose is maintained
• Eventually, B cell compensation becomes inadequate and there is progression
to hyperglycemia
T2DM
• The fraction of glycosylated hemoglobin
in circulating red blood cells
• Reflects the degree of hyperglycemia
during the preceding 6-8 weeks
HbA1C
___vascular disease
• Retina –diabetic retinopathy
• Kidneys –nephropathy
• Peripheral nerves - neuropathy
Microvascular disease
\_\_\_\_ vascular disease • Heart - myocardial infarction • Brain - stroke • Peripheral vascular disease –lower extremity gangrene
Macrovascular disease
• A dermatosis characterized by velvety,
papillomatous, brownish-black,
hyperkeratotic plaques, typically of the
intertriginous surfaces and neck
• May be associated with insulin resistance
(cutaneous marker for type 2 diabetes)
• May be associated with internal malignancy
Acanthosis nigricans
- Oral Complications
- Infections
- Candida sp.,
- Mucormycosis
- Bacterial
- Slow healing
- Gingiva
- enlargement, erythema
- Subjective xerostomia
- Parotid gland enlargement
DM
• Regenerative • Remove 60% • Minimal change in function • 4-6 weeks for almost total regeneration of mass • The key is the hepatic reticulum • Type 4 collagen • Fibrosis= Types 1 & 3 collagen
Liver
• Metabolic • Glucose homeostasis • Synthetic- plasma proteins • Albumin, VLDL, LDL, PT, Fibrinogen • Storage • Glycogen • Triglycerides • Iron, Copper • Vitamins- A, D, K • Degrades/Detoxifies • Phase 1 oxidation • -OH, -COOH • Cytochrome p450 • Phase 2 conjugation • Glucuronic acid= Soluble • Exocrine • Bile (1L/d) • Endocrine • D3 to 25-hydroxy-cholecalciferol • T4 to T3 (active) • GHRH • Insulin & glucagon degradation
Liver
Causes of \_\_\_\_\_\_ • One of top 10 causes of death • ETOH • Infection (HBV, HCV) • Biliary disease • Iron overload (Hemochromatosis) • Autoimmune hepatitis • 10% idiopathic
Cirrhosis
\_\_\_\_ characteristics • Diffuse fibrosis and conversion of normal architecture into abnormal nodules • Bridging fibrosis • Parenchymal nodules • Micro (3mm);Macro • regeneration • Entire liver architecture effaced
cirrhosis
\_\_\_\_ clinical consequences: • Ascites • Formation of portosystemic venous shunts • Congestive splenomegaly • Hepatic encephalopathy
Portal hypertension
- NON-SPECIFIC sign of liver dysfunction
- Retention of bile (>2.0 mg/dL)
- Hepatitis
- Obstruction (cirrhosis)
- Accumulation of conjugated bilirubin
- Hemolytic anemias
- Accumulation of un-conjugated bilirubin
- Cholestasis (Lack of flow of bile)
- Retention due to obstruction or hepatocyte dysfunction
- Serum Alk Phos elevated
Jaundice
Is jaundice a disease?
No
Causes of \_\_\_\_ Disease • Alcohol related • Drug related • Infectious (HCV) • Metabolic • Neoplasms • Autoimmune
Liver disease
ETOH causes 60% of Chronic Liver Disease • ETOH accounts for 40-50% of deaths due to cirrhosis • 5th leading cause of death • Forms of liver disease • Hepatitic steatosis • Alcoholic hepatitis • Cirrhossis
Alcoholic liver disease
\_\_\_\_\_ damage • Tetracycline • Anti-neoplastic agents • Mushroom toxins • Amanita Phalloides • Carbon tetrachloride • ETOH • Microvesicular fatty change • Macrovesicular fatty change • Fibrosis/cirrhossis • Diffuse/massive necrosis • Centrilobular necrosis • Macrovesicular fatty change • Fibrosis/cirrhossis
Hepatocellular damage
\_\_\_\_\_\_ Hepatitis • Self limiting • No carrier state • Life long immunity • Vaccine • Epidemics • Rare fatalities (0.1%)
HAV
\_\_\_\_\_\_ Hepatitis • Prolonged incubation • Chronic carrier state • Increased risk of HCCa • Vaccine- Anti-HBs • 2 Billion alive today will be infected
HBV
\_\_\_\_\_\_ Hepatitis • Similar to HBV, but... • More cirrhosis risk • Used to be transfusion related • IV drug related • Early Tx hopeful for cure
HCv
\_\_\_\_\_\_ Hepatitis • Needs HBV (HBsAg) • Coinfection of B & D at same time • low chance • Super-infection of a carrier of HBV that gets a new HDV • More likely
HDV
• Excessive accumulation of Iron • WNL= 2-6 gms (only 0.5gm in liver) • Males 5-7:1 ( earlier than females) • 5th-6th decades • Iron deposition in liver, pancreas, myocardium, skin, joints
Hemochromatosis
- Fatty liver changes & encephalopathy in Kids (<4 yo)
- Associated with viral infection
- Begins as pernicious vomiting 3-5 days s/p virus
- Lethargy, irritability, hepatomegaly
- Mitochondrial hepatopathy (LOF)
Reye syndrome
• AR disorder of Copper metabolism • Chr 13 • 1:30,000 • Accumulation in Liver, brain, & eye • Normal uptake but: • Failure to enter circulation as ceruloplasmin • Inability to be excreted in bile • Unbound copper spills into circulation • Hemolysis • Diagnosis • Onset prior to age 6 • Elevated hepatic copper, low serum ceruloplasmin, high urinary copper • Acute/Chronic hepatitis • Neuropsychiatric • Behavioral changes • Parkinson-like • Pychosis • Kayser-Fleischer rings
Wilson disease
- Geographic distributions
- Asia, Africa
- 20-40 yo
- 50% w/o cirrhosis
- West much lower (8-30x less)
- Seldom before 60 yo
- 90% w/ cirrhosis
- Cirrhosis (alcoholic)
- HBV (200x), HCV
- Aflatoxin (Aspergillus flavus)
Hepatocellular Carcinoma
Hepatoma
- Located in the upper right quadrant
- Stores bile
- 50mL
- Releases bile
- Fat digestion
Gallbladder
______ Cholecystitis
• Acute inflammation
• Obstruction of the neck or cystic duct
• Absence of gallstones
Acute
______ Cholecystitis
- Sequel to repeated bouts of acute cholecystitis
- Absence of acute cholecystitis
- Gallstones
• Chronic