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Pathophysiology Test 3 USF


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Effect smoking has on cilia of respiratory system
Paralysis, therefore you can't move the "gunk" out efficiently
Upper respiratory System
Everything but the lungs themselves
Characteristics of Upper Respiratory Infections
acute inflammation
they increase your susceptibility to bacterial infections:

streptococcal nasopharyngitis
bacterial sinusitis (inc. susceptibility to meningitis)
otitis media (eustachian tube)
thin, transparent, double layered serous membrane that lines the thoracic cavity (parietal) and encases the lungs (visceral)
Cell structures of Bronchial Tree:

Bronchus, Bronchiole, Alveolus
Bronchus - goblet cells, mucous glands, mucous blanket, pseudostratified epithelium

Bronchiole - simple epithelium, no goblet cells, no mucous blanket

Alveolus - simple squamous cells, increased gas exchange
Pathways microorganisms use to enter the lungs and cause infection
dissemination from distant infection sites in the body (through blood) such as GI infection or any other organ
Are lungs normally a sterile environment?
First flu pandemic facts
20-40 million people killed
started in kansas w/ one person
Influenza caused by
orthomyxoviridae family of viruses
RNA genome
Influenza incubation period
up to 4 days
Flu symptoms
high fever
extreme fatigue
dry, unproductive cough
sore throat
runny or stuffy nose
extreme muscle aches
TYPE A Influenza Virus
most common, most severe
can infect multiple species
virtually all type A can affect birds
Type A influenza subtypes characterized by
hemaglutinin and neuraminidase surface antigens
2006 influenza strains in vaccine
Type B influenza
very mild
antigenic DRIFT
every flu season
very slight changes in surface antigens
last years antibodies may still protect you
antigenic SHIFT
different subtype of virus forming rapidly
new antigens
no previous immunity
spread quickly among birds in markets
Method of flu shot vaccine
contains killed virus
nasal spray flu vaccine
live, weakened flu virus - not for the immune compromised. 5-49 years old, not pregnant, healthy.
Bird Flu Strain
Pneumonia Facts
one of the leading causes of death in the United States

Most common cause of death due to an infectious disease
Community Acquired Pneumonia
mostly viral

most commonly acquired viral pneumonia

If bacterial, most likely hospital acquired S. pneumoniae. Diplococcus w a slippery polysaccharide capsule makes it a hard bacteria to fight.

This bacteria also causes: otitis media, sinusitis, meningitis.
Pneumonia vaccine for adults
23-valent pneumococcal vaccine
Pneumonia vaccine for children
7-valent pneumococcal vaccine
Hospital acquired pneumonia
20-50% mortality - mostly immunocompromised patients in nursing homes, prisons, etc.

90% due to bacteria:
Pseudomonas aeruginosa, S. aureus, Serratia sp., Klebsiella sp. (alcoholics prone to this), E. Coli (infants prone to this)
Risk factors for hospital acquired pneumonia
Mechanical ventilation and airway instrumentation (both of these work against your innate immune systems goal to keep these areas sterile)


Chronic lung disease
Pneumonia is a major cause of death in the immunocompromised person because
they have a decreased B-Cell count due to decreased humoral immunity, therefore they are at increased risk of bacterial infections
Nasopharyngeal defenses

Function & Factors that impair their effectiveness
Fx - remove particles from the air, contact with IgA protects against infection

Impaired by - IgA deficiency, hay fever, common cold, trauma to the nose
Glottic and cough reflexes

Function & Factors that impair their effectiveness
Fx - prevent aspiration into tracheobronchial tree

Impaired by - loss of cough reflex for any reason (ie stroke), neuromuscular disease, abdominal or chest surgery, nasogastric tube
Mucociliary blanket

Function & Factors that impair their effectiveness
Fx - remove secretions, microorganisms, and particles from respiratory tract

Impaired by - smoking, viral diseases, chilling, inhalation of irritating gases
Pulmonary Macrophages

Function & Factors that impair their effectiveness
Fx - remove microorganisms and foreign particles from the lung

Impaired by - chilling, alcoholic intoxication, smoking, hypoxia
Mycobacterium Tuberculosis
3 million/yr. die worldwide from TB
rod shaped bacterium
waxy capsule (hard to phagocytize)
airborne via resp. droplets

can affect any organ
causes caseous (cheesy) necrosis

bacteria has evolved to be able to live inside macrophage
Tuberculin test indicates
exposure, not active infection
Diagnosis of active infection requires
visual ID of organism in resp. tract secretions.
TB is miliary, meaning that it seeds all over the lung. This is the most severe form of TB, and easily disseminates to other organs.
Cavitary TB
essentially eats craters in lung tissue
FALSE NEGATIVES in HIV+ and TB+ people are due to
decreased T-cell count, you cannot see the body reacting to the TB
Ghon's complex
Caseous necrosis in the center, T-cells and macrophages cannot destroy so they wall it off. Creates a dormant lesion that can come back later under stressful conditions
Primary TB
T cell response - development of cell-mediated immunity - positive skin test
granulomatous inflammatory response
Ghon's complex
Healed dormant lesions

under stress, this can move to reactivated or secondary TB
Secondary TB
can begin with stressful conditions and Ghon's complex, or upon reinfection
Treatment for active TB infection
Rifamate and Rifater
Treatment for exposure but not active TB infection
Calmette-Guerin vaccine - attenuated strain of TB - high dose gets immune system going strong
Chronic Obstructive Pulmonary Disease
Characterized by difficult expiration, air trapping

includes asthma (type 1 hypersensitivity), chronic bronchitis, emphysema

Manifestations of COPDs (mostly related to emphysema and bronchitis)
inflammation, fibrosis, hypertrophy of submucosal glands (all of these cause obstructions)

loss of elastic tissue (lungs can't recoil, more likely to trap air)
loss of alveolar tissue - can't exchange gases well, hypoxia, excess CO2
enlargement of airspaces distal to the terminal bronchioles with destruction of the alveolar and capillary walls

affects smokers, those genetically deficient in alpha1-antitrypsin (early onset, non-smokers)
chronic bronchitis
excess production of tracheobronchial mucus causing productive cough FOR AT LEAST 3 MONTHS DURING 2 CONSECUTIVE YEARS

inflammation of the bronchi caused by irritants or infection (smoking)
Emphysema appearance
barrel shaped chest (caused by air trapping)
chronic bronchitis appearance
possibly cyanotic
difficulty with inhalation as well as exhalation
Tumors of the respiratory tract
very poor survival rate, 14% for 5 year survival.
Respiratory tract tumor risk factors
Lifetime smoker has 20-30% inc. risk compared to nonsmoker

more smoking = more risk (dose response relationship)

20+ components in tobacco modify DNA, and all cancers are due to DNA error
Manifestations of resp. tract tumor
upper respiratory infections
superior vena cava syndrome (lung tumor suppresses superior v.c., which slows blood return to the heart)
shoulder and scapular pain (brachioplexus nerves - tumor sometimes metastasizes here, causes great pain!)
Squamous cell carcinoma

signif. tumore growth and lymphatic spread before diagnosis

hyperparathyroidism (a manifestation - alveolar cell begins to fx as a parathyroid cell, which leaves you with increased calcium levels)
most common RT tumor
early metastasis
non smokers
peripheral (solitary periph. lesion)
mostly women
Large Cell carcinoma
rapid growth rate in RT
early and widespread metastasis
Small Cell carcinoma
very serious, usually systemic by time of diagnosis

paraneoplastic manifestation (will behave like a number of diff. cell types - ACTH, ADH, PTH, etc.)

strong assoc. with smoking

death possible w/in 3 mos. of onset
parathyroid hormone

regulates calcium levels in the body
adrenocorticotropic hormone - acts on cortex of the adrenal gland and controls release of glucocorticoid hormones
anti-diuretic hormone
water retention in body, more ADH = less urine output
most common metastasis sites for respiratory tract tumors
Bone, brain
Laryngeal cancer
voice box inserted
1-2% of all cancers in US
men, smokers, 50-75 years
squamous cell carcinoma of larynx
progressive hoarseness
generally good prognosis if caught early
layers of the GI tract
Lumen - mucosa - submucosa - muscularis serosa
difficulty swallowing
Causes of dysphagia
diverticular herniations (esophageal)
scleroderma (autoimmune attack on smooth muscle of esoph)
neural disorders (CVA - esp. if stroke altered function of cranial nerve v, IX,X or XII) and (Parkinson's Disease)
paralysis (no peristalsis) of the lower 1/3 of the esophagus, w/o peristalsis, stomach doesn't open properly, food backs up
Mallory-Weiss Syndrome
Alcoholics and Bulemics mostly

longitudinal tear in the mucosa or submucosa near the gastroesophageal junction

due to incomplete relaxation of the esophageal sphincter during vomiting

administer vasopressin into the superior mesenteric artery to stop the bleeding post-tear
Gastroesophageal Reflux

manifestations: heartburn, chest pain, regurgitation

inflammation and ulceration of the epithelium of the esophagus

increased risk of metaplasia (Barrett's esophagus) and fibrosis (can lead to dysphagia)

normal esophagus = stratified squamous epithelium

GERD esophagus = simple columnar epithelium (this is Barrett's esoph - takes on characteristics of stomach lining to handle the acid contents)
Hiatal Hernia
protrusion of the stomach through the diaphragm and into the thorax

2 types - sliding and paraesophageal
sliding hiatal hernia
most common, less severe, part of stomach slips through diaphragm opening at esophagus

caused by high abdominal pressure - pregnancy, obesity
paraesophageal hiatal hernia
idiopathic - trauma maybe??

diaphragm tears slighty, new opening, a bit of stomach slips through opening.

more severe
Carcinoma of the esophagus
could be squamous cell carcinoma or adenocarcinoma

95% die w/in 2 years of Dx
squamous cell carcinoma of esophagus
90% of esophageal cancers

most originate in middle to lower regions, discovered during investigation of nonspecific upper GI discomfort

usually chronic smokers et alcoholics
adenocarcinoma of the esophagus
usually those with Barrett's esophagus (lining has changed to simple columnar from simple squamous to handle the acidity fo the stomach contents)
secretes pepsin and HCl (HCl secreted by parietal cells)

chief cells and parietal cells make all gastric juices

pepsin breaks down proteins
stomach mucosal barrier
epithelial cells - tight junctions

parietal cells - secrete H+ and HCO3- at 1:1 ratio

Mucus - protects against actions of pepsin
Acute gastritis
aspirin and/or alcohol compromise epithelial barrier in stomach, change consistency of mucus blanket

vague abdominal discomfort

some bleeding

may involve some erosion
Chronic Gastritis
inflammation, thinning and degeneration of the stomach wall - gastric atrophy

usually elderly
autoimmune gastritis
fundus and body of stomach
more severe

pernicious anemia
hypochlorhydria - more basic

increased risk of developing gastric cancer

chief or parietal cell antibodies might be present
Helicobactor pylori
gram neg rod shaped bacteria
multiple flagella

colonizes the mucus-secreting epithelial cells of the stomach, secretes urease which produces ammonia
eradicate H. pylori
acid-neutralizing agents, acid-inhibiting agents (proton pump inhibitors)
avoid NSAIDs
bland diet
Helicobactor Pylori Gastritis
most common cause of gastritis

may lead to gastric atrophy, peptic ulcer, gastric adenocarcinoma

antibiotic therapy removes risk
Peptic Ulcer Disease
not confined to stomach - anywhere that can come in contact with peptic secretions

mucosal ulceration (caused by h. pylori, NSAIDs and aspirin) that may extend through the muscularis of the:
lower esophagus
Complications of Peptic Ulcer Disease

perforation - can perf. adjacent organs as well (ie duodenum to pancreas)

intestinal stenosis - scar tissue narrows lumen of duodenum
Carcinoma of the Stomach
caused by nitrosamines??

adenocarcinomas - nonspecific symptoms, metastasize to lymph and liver, 5 yr survival rate 10-15%

very high in asian countries due to smoked fish in diet
Malabsorption Syndrome in small and large intestine
inadequate intraluminal digestion

mucosal absorptive defects

impeded transport of nutrients
Pancreas endocrine function
insulin and glucagon
pancreas exocrine function
amylase, lipase and trypsin produced by acinar cells of the pancreas

sent to duodenum through the pancreatic duct and help in lipid digestion
Cystic fibrosis complication with malabsorption
normal enzymes are produced by the pancreas, but due to mucus blockage in the pancreatic duct, they never make it to the duodenum to assist in digestion and absorption
liver function
makes bile, which goes to gallbladder then to duodenum through the hepatic duct.

bile emulsifies fats, breaks them down and makes it easier for the lipase from the pancreas to work
Inadequate intraluminal digestion
pancreatic insufficiency (cystic fibrosis, chronic pancreatitis, pancreatic carcinoma, pancreatic resection)

lactase deficiency - (congenital defect most common in blacks, fermentation of undigested lactose in intestine)

liver disease (affects bile formation)
Mucosal absorptive defect
celiac sprue - normal villi look like scrunched up sheet - with celiac sprue, look like its been flattened out

aka gluten-sensitive enteropathy

hypersensitivity (T-cell) to gliadin in dietary grains

symptoms appear early in childhood, possibly genetic component
Impeded transport of nutrients
lymphoma within the gastrointestinal wall increases lymphatic pressure which inc. BP

congestive heart failure causes backwards pressure which makes it harder for nutrients to move out of bloodstream, digestive tract

intestinal ischemia
inflammatory bowel disease
usually females Dx in highschool

ulcerative colitis, crohn disease

possibly life threatening

Common features:
inflamm. of bowel
unknown causitive agent
family tendencies
remissions and exacerbations of diarrhea and wt. loss
systemic manifestations: axial arthritis, hypercoagulation of blood
Crohn's Disease
creates cobblestone pathway appearance in LI and SI

granulomatous inflammation

genetic susceptibility locus: chromosome 16 ibd1 gene --> NOD2 protein (controls how you deal with LPS bacteria, can't take care of properly with macrophages)

Treated w/ infliximab (Remicade)

affects mucosa and submucosa
Ulcerative Colitis
Red velvet appearance in LI & SI
affects mucosa only

ulceration of the colonic mucosa in the rectum, sigmoid colon

risk fac: FH, jewish descent, caucasian
Diverticular disease
in LI, thin layer of longitudinal muscle w/ multiple weak areas.

diverticula = outpouchings of mucosa through the muscularis of the colon wall

prob. results from high intraluminal pressure on the areas of the weakness in the bowel wall

inflammation of diverticula = diverticulitis

rupture = intestinal contents in peritoneum = peritonitis

low fiber diets are the strongest linking factor due to unequal intraluminal pressure
most common surgical emergency of the abdomen

usually young adults

obstruction to the opening of the appendix leads to inflammation, leads to rupture, which leads to peritonitis
Intestinal neoplasms
20% genetic causes (like colon cancer)

rest dietary related - high fat, low fiber. fat possible carcinogen after digestion, low fiber means it sits there for a while
pathogenesis of intestinal neoplasm
epithelial cells do not divide properly
loss of tumor suppressor gene
deregulation of normal proliferation
means cells proliferating not just in the crypts of the LI epithelium, but all over
plus limited apoptosis

end result accumulated cells, create polyps

eventually, polyp cells continue to proliferate and lose control over that proliferation, become malignant
colorectal cancer
risk factors
advanced age (50-70 yrs, 90% over 50 yrs)
family Hx
ulcerative colitis
Chrons disease
colorectal cancer
if limited to mucosa and submucosa, 80-100%

if all layers but no lymph 50-70%

if all layers and local lymph 30-50%
colorectal cancer
(+) fecal occult test

blood test - carcinoembryonic antigen (CEA) normally only produced by embryo, not specific to colon cancer, but only present in blood when a cancer is present somewhere
Acute viral hepatitis
inflammation of the liver
differs in modes of transmission, incubation period, degree of damage and existence of a carrier state

most prevalent liver disease in the world
carrier of Hepatitis characteristics
harbor virus
Hepatitis A
vaccine available?
transmission: fecal/oral, parentoral, body fluids

fever, malaise, dark urine, jaundice

not chronic
no carriers
vaccine available (3rd world travel)
Hepatitis B
vaccine available?
trans: body fluids,parentoral

fever, malaise, dark urine, jaundice

possibly chronic, yes carriers, yes vaccine
Hepatitis C
vaccine available?
trans: parentoral, body fluids

asymptomatic, nonspecific

chronic possible, yes carriers, no vaccine avail.
Hepatitis B
250K new cases/yr, 1 mill. carriers

if mother has, can kill fetus/infant

Blood marker test - HB surface antigens produced by infected hepatocytes and
then released into serum

when chronic, only liver transplant can cure. messes up bile formation, glycogen storage, metabolism
living liver donors
possible! thanks to compensatory hyperplasia, you regenerate the donated portion of your liver
mechanism of injury from viral hepatitis
direct cellular injury to each hepatocyte
can be caused by viral hep, alcoholism

irreversible inflammatory disease disrupts liver fx and structure

scar tissue and liver cell nodules formed (cobblestone) replace normal parenchyma (normal cells)

incurable except by liver transplant
Portal Hypertension
complication of cirrhosis

portal takes nutrition rich blood from intestines through liver to be cleaned then dumps in vein to go to heart. whhen liver messed up, increased pressure due to nodules

inc. pressure in peritoneal cavities can lead to ascites or abnormal abdominal fluid, or portosystemic shunting of blood.
portosystemic shunting of blood
this is not good, cause collateral blood routes are formed, but then blood isn't cleaned by liver before dumping into circ. system

causes caput medusa (blood vessels look like snakes)
esophageal varices (varicose veins on esophagus) which cause blood backup
collateral circ - hemorrhoids

increased ammonia in circ. toxic to CNS, hepatic encephalopathy
complication of cirrhosis

anemia due to RBC's blocked up, Thrombocytopenia due to platelets backed up
leukopenia due to WBC backup
alcoholic cirrhosis
15+ yrs heavy drinking

smooth ER in hepatocytes makes "microsomal - ethanol oxidizing system" which makes
alcohol --> acetalaldehyde + free radicals

acetalaldehyde promotes collagen synthesis which is an ingredient of fibrotic tissue, which causes cirrhosis

acetalaldehyde prevents mitochondria from producing ATP, so can't run active processes like ion pumps
H+ ions accumulate w/o operating pumps, H+ ions used to make lipids, leads to fatty liver (steatosis)
why does liver failure cause hypoglycemia?
normal liver responsible for glycogen storage. if you can't store the glycogen, you will be hypoglycemic
why does liver failure cause encephalopathy?
in liver failure you can't metabolize excess amino acids, which leads to a buildup of ammonia, which causes encephalopathy
why does liver failure cause hypoalbumenia?
liver makes albumin normally, when not functioning it doesn't.

albumin normally prevents edema, so w/o it you get edematous, ascites.

dec. clotting factors not being produced by liver causes excess bleeding
why does liver failure cause improper absorption of fat soluble vitamins?
liver norm. produces bile salts which help break down lipids. if not producing, lipids don't break down and then can't dissolve these vitamins
why does liver failure cause jaundice?
can't get rid of the bilirubin if liver not functioning, builds up and spills into tissue and causes jaundice
Primary liver cancer
rare - liver cancer usually metastasized from elsewhere

risk fact: aspergillus in moldy hay, cirrhosis, chronic hepatitis B,C,D, p53 tumor suppressor gene mutation

very poor prognosis

serum alphafetoprotein blood marker produced by cancerous liver cells
Gallstones (cholelithiasis)
cholesterol stone - bile supersaturated w/ cholesterol. most common stone, amer. indian descent, overweight and high cholesterol risk fact., look like hard piece of indian corn

Pigmentary stones - not as common, exclusive to sickle cell population, look like pieces of charcoal. bile supersaturated w/ bilirubin
complications of gallstones
obstructions of common bile duct (normally bile from GB and liver goes through here) by stones leads to obstructive jaundice

infection and obstruction of outflow from degraded mucosa leads to rupture which leads to bacterial peritonitis
inflammation of gall bladder when gallstones injure mucosa ultimately leads to entry of enteric bacteria into the gall bladder through irritated area

could rupture, lead to bacterial peritonitis
acute pancreatitis
could be life threatening

acinar cells produce enzymes which go through panc. duct to duodenum.

rapid onset of inflammation of pancreas leads to rupture, releases enzymes which then start breaking down your other organs that are proteins and lipids

older than 50, alcoholic risk factor

increased serum amylase and lipase = positive

exocrine insufficiency
Chronic pancreatitis
injury --> inflammation --> repair over and over, tons of fibrotic tissue replacing normal pancreatic parenchyma (normal cells)

high fat diet, alcoholics risk

in a few cases preceded by actue pancreatitis, but not usually

endocrine insuff. - enzymes leak out of duct, insuff.

exocrin insuff. - lost islet cells means not enough insulin made means can't make glucagon means hypoglycemia
pancreatic cancer
bad, painful way to go. poor prognosis

95% adenocarcinomas (glandular) of pancreatic duct

significant cause of death in US

lack of enzymes, can't digest food properly, death within 2 yrs of diagnosis

risk: smoking, alcohol, high fat diet, chronic pancreatitis, age 50+

painful because it entraps nerve fibers
hormones - receptor cell locations
some receptor cells are on the surface of the plasma membrane

some cholesterol based hormones like estrogen and testosterone travel through plasma membrane to receptors in the nucleus
"releasing hormone"
this means it comes from the hypothalamus
hormone travel from hypothalamus
through the cell bodies and down the long axon - swollen ends of the axons in the neurohypophysis store the hormones in the hypothalamus
Hypothalamus hormones:
ADH - antidiuretic hormone
Oxytocin - acts on smooth muscle of the uterus
hypothalamus protected by:
sella turcia, bone saddle. when absent, parts of pituitary gland missing, hormone deficiency present
axons form stores of hypothalamus hormones

posterior lobe of pituitary gland
anterior lobe of pituitary gland

endocrine cells - make AND secrete hormones, can dump directly into bloodstream. If there is ischemia in this area, it is the adenohypophysis that is affected first

makes GH, TSH, ACTH, FSH, LH and prolactin
growth hormone - acts on muscles, bones, cartilage and all body organs, promotes protein synthesis and fat metabolism
thyroid stimulating hormone - secretes follicle cells T3 and T4

increase metabolism, necessary for fetal growth and development, increase protein and bone turnover
follicle stimulating hormone. target ovaries, controls stimulation of follicle to release egg
leutinizing hormone, controls sperm production, ovulation cycle
targets mammary glands and controls lactation functions
when does adenohypophysis (anterior pituitary gland) secrete hormones?
after receiving a releasing hormone from the hypothalamus
tumor or infarction in the anterior pituitary "pan hyperpituitarianism"

causes - tumor, infarctions, empty sella turcia syndrome, hypothalmic disorders: GRH growth releasing hormone deficiency (stroke damages hypothalamus, GRH not released so GH can't be secreted)
order in which hormone production is lost in hypopituitarism
Go Look For The Adenoma

Pituitary Dwarfism
not enough GH to cause growth

proportionally correct

can be managed if caught early before epiphyseal plates close off - given recombinant GH
Old method of giving GH
used to grind up cadaver pituitary glands and feed, people got Cruetzfeld Jakob disease (human mad cow)
hypersecretion of GH before epiphyseal plates close off

8-9' tall

if not treated, will develop acromegaly - thickening of bones, organs, etc., when GH continues to be released in adulthood

drugs can counteract early on
slowly progressive
increased connective tissue and bone proliferation

hypersecretion of GH during adulthood

untreated lowers life expect. due to hypertension and DM

DM due to glycogen breakdown even when not necessary, inability to take glucose into cell, means high serum glucose or hyperglycemia

deep voice, tongue hanging out
thyroid gland
anterior to trachea

T3 (tri-iodothyronine) and T4 (thyroxine)secreted depending on # of iodide, and in response to thyrotropin releasing hormone TRH from hypothalamus
hypothalamus - pituitary - thyroid feedback system
hypothalamus secretes TRH to the anterior pituitary, which secretes TSH to the thyroid gland which sends t3 and t4 to the target organs. when t3 and t4 levels are high, the hypothalamus and anterior pit are inhibited from secreting more
actions of thyroid hormone
increased metabolism:
rate of protein, fat and glucose use increases
increased oxygen consumption
inc. metabolic waste products

high metabolism = increased respiratory rate

in kids:
inc protein synthesis
necessary for mental dev.
necessary for attainment of sexual maturity
Congenital hypothyroidism
qenetic malfunction prevents body from making and or secreting a thyroid hormone

decreased thyroid tissue, didn't completely grow

can lead to cretinism

treatable w/ supplemental hormones, part of standard newborn screening
untreated congenital hypothyroidism, preventable mental retardation
acquired hypothyroidism
most common disorder of thyroid function
more common in women

manifest: sluggish, fatigued, intolerance of cold, low BMR, bradycardia, impaired memory, low t3 and t4 levels

can lead to myxedema

treatable with thyroid supplements
untreated acquired hypothyroidism

can lead to a coma. accumulated polysaccharides under eyes in advanced state - look droopy
graves disease
lead cause of hypothyroidism
due to stim. of the thyroid w/ antibodies against the TSH receptor which leads to overproduction of thyroid hormones.

TSH receptor actually being activated by an antibody, which causes increased production of T3 and T4 even though you have plenty of it already

more common in women (5:1)

develop. linked to predisposition to autoimmune disorders, external stressors
Graves disease blood test results
T3 and T4 - high (still being made because TSH receptors being triggered by antibody)
TSH - low (no longer being released because of high t3/t4 levels)
TRH - low (also not being released)
graves disease manifestations
neurologic: irritable, restless

reproductive: amenorrhea, impotence

cardiovascular: tachycardia, heat intolerance

sensory: exopthalmus (large eyes) due to hyperstimulation of extrinsic eye muscles and lipopolysaccharide accumulation behind eyes
treatment of graves disease
radioactive iodine, destroys part or all of the thyroid gland

subtotal thyroidectomy (removal of portion of thyroid)
thyroid carcinoma
most common endocrine malignancy
less than 1% of all cancers in US
risk: exposure to ionizing radiation, esp. during childhood - so leukemia and lymphoma patients would be at increased risks from their previous treatment plans
Adrenal cortex zones
glomerulosa of adrenal cortex
secretes mineral corticoids such as aldosterone - controls potassium and sodium levels
fasciculata of adrenal cortex
secretes glucocorticoids such as cortisol which regulates glucose metabolism
reticularis of adrenal cortex
secretes gonadocorticoids such as adrenal estrogens and androgens which initiate puberty
pathway of Adrenal stimulation
hypothalamus releases CRH (corticotropic releasing hormone) which makes the anterior pituitary release ACTH, which binds to receptors in the cortex of the adrenal gland and causes release of corticoids
medulla of adrenal gland
in charge of epinephrine and norepinephrine
cushing syndrome
hypercortical disease
too much cortisol released, possible adrenal tumor
cushing disease
hypercortical disease - too much cortisol specifically due to too much ACTH (prob. caused by pituitary tumor)

could be a result of many years of asthma steroid treatment

excessive production of cortisol causing adrenal or pituitary tumor

manifest: moon shaped vface, thin skin, accumulation of fat, altered sex characteristics
endocrine fxs of pancreas
pancreas is 1% endocrine

islets of langerhans-
beta cells sec. insulin
alpha cells sec. glucagon
delta cells produce somatostatin
release inhibited by high glucose levels

primary target is hepatocytes for glycogenolysis, gluconeogenesis

inc glucose inhibits alpha cells from releasing glucagon, because response to glucagon is to lyse glycogen which would increase serum glucose
glycogen to ATP chain
glycogen broken down through glycogenolysis which results in glucose which is broken down by glycolysis which then enters kreb's cycle and the electron transport chain and results in ATP
glucose metabolism
energy requirements predominantly met by glucose

produced from glycogen stores
manufactured from substrates
supplied from diet
hormone of "fed" state, causes uptake of glucose by cells

secretion stimulated by high conc. of glucose in the blood

facilitates transport of amino acid into target cell --> protein synthesis
high level of blood glucose
stimulates depolarization in the beta cell of the pancrease, which causes insulin secretion

cell membranes impermeable to glucose, require the glucose transporter
glucose transporters
GLUT -1, GLUT -2, and GLUT-4

facilitated diffusion
NOT insulin dependent glucose transporter, found on all cells (especially at blood/brain barrier)
NOT insulin dependent glucose transporter, found on hepatocytes and beta cells of pancreas
Insulin DEPENDANT glucose transporter found especially on skeletal muscle and adipose tissue
action of insulin dependent transporter
insulin mobilizes Glut-4 to the membrane surface to allow glucose transport across membrane and into the cell

exercise helps, skeletal muscle opens up like a drain and naturally takes in glucose from blood for energy - naturally lowering blood glucose levels
Diabetes Mellitus
6th leading cause of death

when poorly managed, increased risk for:
heart disease, end stage renal dis, blindness, amputation, compl. of pregnancy, stroke
Type 1 DM
immune mediated, idiopathic

charact. by destruction of beta cells in the pancreas

most common diag. between 5 and 20 yrs, sudden onset

more prev. in caucasians, male to female ratio approx. equal

low twin concordance, low serum insulin
immune mediated type 1 DM
this is the major form of type 1

autoimmune attack on the beta cells,

genes of MHC (major histocompatability comples) on chromosome 6

exogenous insulin required
idiopathic type 1 DM
no evidence of autoimmunity at all, but still destroying beta cells, method unclear

exogenous insulin required
Type 2 DM
resistance to the action of insulin on periph tissues and/or secretory defect in insulin production

too much of the same message, not listening anymore

non caucasians and over 30 yrs
more prev. in women
risk: age, sedentary lifestyle, obesity
indentical twins: 100% concordance


diet and exercise controlled, oral hypoglycemics or exogenous insulin
poorly managed diabetes - starving in a sea of plenty
plenty of glucose available in the blood, but no way to take it into the cells properly
excess urination
excess hunger
excess thirst
complications of DM
damage may be due to:

excess intracellular sorbitol? normally glucose breaks down into sorbitol and then fructose, but the second step of sorbitol to fructose is very slow, which leads to high sorbitol levels

formation of adv. glycation end products? abnormal metabolite - glycation end products build up in the capillaries and cause damage

decreased oxygen delivery? RBC oxygen unloading errors - glucose possibly linked to RBC oxygen unloading mechanism?
Macrovascular complications of unmanaged DM
cardiovascular disease

not managing DM lowers HDL's which causes cholesterol accumulation and forms atheromas

resp. for 1/2 of all deaths in diabetics
Microvascular complications of unmanaged DM
thick basement membrane which compromises 02 delivery

retinopathy - macular degeneration, hemorrhages and aneurysms

nephropathy - thick BM = damaged glomerular capillaries which don't filter well, too many holes eventually end up with protein in urine
Neuropathic complications of unmanaged DM
diabetic neuropathy produces symptoms in 60-70% of diabetics

GI disturbances (slow motility)
bladder dysfunction
sexual dysfunction

lack of sensation in feet - leads to foot ulcers
Gestational DM
2-5% of pregnancies

while pregnant, require 2-3 times the insulin normally required

this is an inability to meet that increased insulin requirement

placental hormones occasionally interfere with the insulin response mechanism

can cause macrosomia (big baby)

baby may be hypoglycemic after birth because glucose crosses placental barrier and baby used to high glucose levels which suddenly aren't there anymore

Deck Info