223 Exam 4 Final Study Guide
Anemias/Heme
● Classification of Anemias
1. -Cytic = refers to size of cell
2. -Chromic = refers to hemoglobin content (strong pigment, not enough content = less red)
3. Anisocytosis = assuming various sizes
4. Poikilocytosis = assuming various shapes
● Types of Anemias and Treatments
1. Macrocytic-Normochromic = Unusually large stem cells (megaloblasts) develop into large erythrocytes.
Hemoglobin content is normal. Results of ineffective DNA synthesis, these die prematurely. Two subclasses both large
size & normal content
A. Pernicious Anemia - Vitamin B 12 deficiency b/c low IF (intrinsic factor)
⮚ Causes: Congenital or due to gastric mucosal atrophy.
o Autoimmune, heavy alcohol ingestion, hot drinks (like tea), smoking, gastrectomy
(removing parts of stomach like from surgery)
⮚ Symptoms: Slow onset and nonspecific symptoms. May develop HF, liver failure
(portal congestion). Weakness, glossitis, paresthesia (abnormal sensations “pins and
needles), splenomegaly, other symptoms of anemia.
⮚ Treatments: Lifelong B12 replacement necessary w/ Cyanocobalamin (form of B12,
watch out for Hypokalemia b/c K incorporated into new erythrocytes).
B. Folate Deficiency Anemia - Folic Acid obtained only from diet. No IF.
⮚ Causes: Dietary deficiency from fad diets, lack of vegetable intake, alcoholism,
pregnancy and lactation.
⮚ Symptoms: Cheilosis (scales and fissures of mouth), stomatitis, painful ulcerations of
tongue, dysphagia, flatulence, diarrhea. Neuro due to thiamine deficiency (tends to
accompany folate deficiency)
⮚ Treatments: Folate replacement-orally, or IM for severe deficiency.
2. Microcytic-Hypochromic Anemias = Abnormally small erythrocytes w/ reduced amounts of hemoglobin
(making the erythrocytes paler).
A. Iron Deficiency Anemia – most common type of anemia
⮚ Causes: Dietary deficiency, Blood loss (2-4ml/day) is enough to cause and can be
from ulcers, esophageal varices, hemorrhoids, ulcerative colitis, cancer, menstruation,
and medications.
⮚Symptoms: Gradual. Signs of anemia + koilonychias (spoon-shaped nails), glossitis,
angular stomatitis; gastritis, irritability, neuromuscular disturbances, numbness,
tingling
⮚Treatment: Find & eliminate source of bleeding. Oral iron replacement.
B. Sideroblastic Anemia - anemias of varying severity. Inefficient iron reuptake �
abnormal hemoglobin w/ iron granules in erythrocytes. Increased tissue levels of iron.
⮚ Causes:
o Acquired: most common, idiopathic; alcoholism, drug reactions, copper
deficiency, hypothermia,
o Hereditary: Rare, X-linked disorders.
o Reversible: alcoholism, folate deficiency, some meds.
⮚ Symptoms: Anemia + iron overload (enlargement of liver and spleen; rare cardiac
rhythm disturbances)
⮚ Treatment:
o Hereditary � Pyridoxine (Vitamin B6); blood transfusions.
o Acquired � remove cause
3. Normocytic-Normochromic Anemias = Normal Size and content, but insufficient in number.
A. Aplastic Anemia – Rare disorder; stem cells cannot proliferate or differentiate. Also,
can be from an altered stem cell environment that inhibits erythropoiesis.
⮚ Causes: Infiltrative disorders of bone marrow, autoimmune diseases, renal failure,
splenic dysfunction, B12 or folate deficiencies, parvovirus infection, exposure to
radiation, drugs, or toxins. May be congenital.
⮚ Symptoms: Anemia w/ thrombocytopenia � hemorrhage, leukopenia � infection
⮚ Treatments: Remove underlying cause; blood transfusions, stem cell transplant,
pharmacologic stimulation of bone marrow.
B. Post-hemorrhagic Anemia
⮚ Causes: Loss of large volume of blood w/ normal iron stores (For whatever reason,
like getting stabbed from fighting your mortal enemy)
⮚ Symptoms: Severe shock, lactic acidosis, or death can occur if blood loss exceeds
40-50% plasma volume.
⮚ Treatment: Blood transfusion; and giving saline, albumin, and plasma
C. Hemolytic Anemia – Destruction of erythrocytes
⮚Causes:
o Acquired: infection, systemic disease, drugs or toxins, liver or kidney disease,
abnormal immune response
o Hereditary: abnormalities in RBC membrane or cytoplasmic contents
⮚Symptoms: Splenomegaly and Jaundice
⮚Treatment: Remove cause; transfusions, splenectomy, steroids, folate
D. Anemia of Chronic Inflammation – results in decreased erythrocyte lifespan, failure of
mechanisms of compensatory erythropoiesis, or disturbance of iron cycle.
⮚ Causes: Associated w/ chronic infections or chronic diseases (AIDS, rheumatoid
arthritis); malignancies
⮚ Symptoms: Fewer and milder than other anemias
⮚ Treatments: No treatment unless symptomatic (tend to be people who don’t get up like older sick
people � usually no symptoms tend pop up)
E. Sickle Cell Anemia – production of abnormal hemoglobin S reacts to deoxygenation
and dehydration � hemolytic anemia
⮚ Causes: Inherited autosomal recessive disorder from origins in equatorial countries
(central Africa, Middle East, and Mediterranean)
⮚ Symptoms: General manifestations of hemolytic anemia, can progress to crises
o Vaso-occlusive crisis: pain, vasospasm, tissue death
o Sequestration crisis: large amounts of blood pooled in liver and spleen, seen only
in children
o Aplastic crisis: due to decreased survival time of sickled erythrocytes
o Other: infection, retinopathy, renal necrosis, aseptic necrosis of femoral head
⮚ Treatment: No cure. Prevent complications by Hydroxyurea (antimetabolite inhibits
DNA synthesis & increases synthesis of hemoglobin F. Can increase hemoglobin
levels and reduce crises)
⮚ Factors that increase sickling: pH; Deoxygenation and dehydration of Hb S �
solidify and stretch into elongated sickle shape. (Reoxygenation returns it to normal
state)
● Polycythemia Vera (PV) = myeloproliferative erythrocyte disorder, excessive production.
Often increased platelets and WBCs w/ splenomegaly
1. Symptoms - increased blood volume & viscosity leading to vessel occlusion, ischemia,
death; plethora (ruddy, red color face, hands, ears, feet, mucous membranes). Increased
volume can increase BP. Aquagenic pruritus (itchy when skin gets wet). Treatment:
phlebotomy; hydroxyurea.
● Infectious Mononucleosis (mono- the kissing disease)
1. Cause - Acute infection of B lymphocytes w/ Epstein-Barr virus (EBV)
2. Transmission - Through saliva like kissing or sharing drinks (kissing disease)
3. Symptoms - Swelling of lymph nodes, spleen, tonsils, occasionally liver, initial flu-like
symptoms (fever, lymph node enlargement, sore throat, fatigue), Later stages can get
splenomegaly-can rupture due to mild trauma (most common cause of death for this
disease); fatigue and malaise can last 1-2months.
● Normal platelet levels = 150,000 mm3 – 400,000 mm3
1. Extra info: Thrombocytopenia is <150,000 but not significant till <100,000. Risk for
hemorrhage (<50,000). Spontaneous bleeding (<15,000) ex. HIT & ITP.
Thrombocythemia is >400,000 but no symptoms until >1,000,000.
● Role of Liver in Clotting = Makes clotting factors. Vitamin K required for synthesis of
clotting factors. (prothrombin, factors II, VII, IX, and X, and proteins C and S).
● Disseminated Intravascular Clotting (DIC) = acquired condition characterized by
widespread activation of coagulation. Both excessive clotting and inability to clot
appropriately.
1. Causes - Malignancy, infections, pregnancy complications, severe trauma, liver disease,
intravascular hemolysis (transfusion reaction, drug induced), medical devices, and
hypoxia and low blood flow states (hypotension, shock)
2. Symptoms - can vary widely
A. Integumentary: hemorrhage and vascular lesions; oozing from puncture sites, incisions,
mucous membranes; cyanosis; gangrene
B. CNS: subarachnoid hemorrhage; AMS
C. GI: occult to massive bleeding, abdominal distension, malaise, weakness
D. Pulmonary: pulmonary infarcts, ARDS, cyanosis, tachypnea, hypoxemia
E. Renal: hematuria, oliguria, renal failure
Liver
● Portal Hypertension = Abnormally High BP in portal system >/=10. Normally 3mmHg.
1. Causes:
A. Intrahepatic: vascular remodeling w/ shunts, thrombosis, inflammation, or fibrosis of
the sinusoids. Can be due to cirrhosis of liver, biliary cirrhosis, viral hepatitis, parasitic
infection.
B. Post-Hepatic: hepatic vein thrombosis or cardiac disorders that impair pumping of right
ventricle (back of blood to portal system)
2. Sequelae – increase in pressure � back up of blood in stomach, esophagus, rectum, and
spleen
A. Varices: Distended, tortuous collateral veins. Occurs in esophageal, stomach abd wall
(caput medusa), rectum (hemorrhoid). If ruptures can be life threatening, precipitate
hepatic encephalopathy.
B. Splenomegaly: can lead to thrombocytopenia
C. Hepatopulmonary syndrome and portopulmonary hypertension: may lead to dyspnea,
cyanosis, fingernail clubbing (manifestation of long term O2 deprivation)
● Ascites = accumulation of fluid in peritoneal cavity (third spacing). Cirrhosis is most common cause.
1. Contributing factors from Cirrhosis � Ascites
A. Increase lymph production (excess fluid in area)
B. Portal hypertension � increase in capillary filtration pressure (less fluid drawn back to
capillary beds � increase in fluid)
C. Hepatocyte failure � Decrease albumin synthesis (keep fluid inside vascular; so, fluid
will leak out) � decrease capillary oncotic pressure + peripheral arterial vasodilation �
decrease effective plasma volume + altered metabolism � increase Renin, aldosterone
& antidiuretic hormone � increase in renal absorption of Na and H2O
D. If you have bacterial peritonitis (from leakage of bowel contents into peritoneal) �
increase capillary permeability � loss of plasma � ascites.
● Hepatic Encephalopathy = complex neurologic syndrome characterized by impaired cerebral function, flapping
tremor (asterixis), and electroencephalogram changes.
1. Causes: Liver failure/dysfunction progression and development of collateral vessels that
shunt blood around liver � less filtering of blood by liver = more toxins to accumulate
like ammonia, inflammatory cytokines, short-chain fatty acids, serotonin, tryptophan, and
manganese.
A. Can be precipitated by infection, hemorrhage, electrolyte imbalances, use of sedatives
and analgesics, and GI bleed.
2. Symptoms: personality changes, memory loss, irritability, lethargy, sleep disturbances;
when SEVERE: can have seizures, coma, stupor, death
● Jaundice (icterus) = Yellow pigmentation of skin caused by increase hyperbilirubinemia
1. Causes
A. Prehepatic: large hemolysis of red blood cells
B. Hepatic: Viral hepatitis, drugs, cirrhosis, or tumors
C. Post-Hepatic: Gallstones or cancer of bile ducts
D. Hepatobiliary mechanisms: when bile ducts blocked � light colored stools; conjugated
hyperbilirubinemia � darkened urine; bilirubin deposition in tissues � yellow skin
● Viral Hepatitis Phases KNOW ALL
1. Prodromal – starts 2 weeks after exposure, ends w/ appearance of jaundice. Fatigue,
anorexia, malaise, N/V, HA, cough, low-grade fever. Highly transmissible
2. Icteric – Lasts 2-6 weeks. Jaundice, dark urine, clay-colored stool. Liver enlarged and
tender. worst jaundice
3. Recovery – resolution of jaundice; liver function back to normal 2-12 weeks after onset of
jaundice.
4. Chronic Active Hepatitis – Persistence of clinical manifestations and liver inflammation in
Hep B & C. Predisposes Pt. to cirrhosis and primary hepatocellular carcinoma (HCC).
(Not a phase but can happen if Pt. don’t recover)
● Hepatitis Chart KNOW ALL
Characteristic Hepatitis A
Hepatitis B
Hepatitis D
Hepatitis C
Hepatitis E
Route of
Transmission
Carrier State
Severity
Chronic
Hepatitis
Prophylaxis
Patho
(not as important,
don’t need to know
this)
Treatment
Fecal-oral
(most
common);
parenteral,
sexual
Mild
Hygiene,
vaccine
Parenteral, Sexual
Can have coinfection of both B
and D; more liver
damage, can lead
to chronic state
+
Severe; may be
prolonged or
chronic
+
Parenteral (?),
fecal-oral, sexual
Can’t get unless
you have B.
Hygiene, vaccine
Hygiene,
hepatitis B
vaccine
+
Severe
+
Hepatocyte
Viral replication,
injury caused inflammation,
by cellular
cellular necrosis
immune
responses
Co-infection w/
HBV, severe cell
injury,
inflammation,
cirrhosis
Symptomatic Interferon-alpha;
support
antivirals
Interferon-alpha
Parenteral,
sexual
+
May be
prolonged or
chronic
+
Hygiene
Practice safe sex
and safe
healthcare
practices
Hepatocyte
injury caused by
immune
response,
inflammation,
fibrosis leading
to cirrhosis
Interferonalpha, antivirals,
Harvoni
Fecal-oral
(ex: poor water,
sanitation, food
worker who
doesn’t wash
hands)
Mild but
Severe in
pregnant women
Hygiene, safe
water
Viral replication,
immune response
causes
inflammation and
cholestasis
Symptomatic
support
● Interferon Alpha vs Harvoni must know
1. Interferon Alpha – naturally made by body. Has antiviral, immunomodulatory, and antineoplastic
actions. Can be manufactured by DNA tech for administration. Must be given parenterally, usually subQ.
A. MOA: binds to receptors on host cell membranes and blocks viral entry into cell; blocks
synthesis of viral messenger RNA and viral proteins, and blocks viral assembly and
release
⮚ Relapse occurs in 50% of Pts when drug is stopped; combo w/ Ribavirin can
improve response rates
B. SE: Flu-like syndrome common (50%), diminishes w/ continued therapy and
acetaminophen can reduce. High risk for depression (especially large doses or
prolonged treatment).
⮚ Prolonged high-dose � thyroid dysfunction, heart damage, bone marrow
suppression. Alopecia (hair loss) and GI effects also occur.
2. Harvoni (Ledipasvir/sofosbuvir) – Oral monotreatment for HCV. Has been combined w/ ribavirin.
Near 100% sustained virologic response. Very expensive $$$
A. MOA: ledipasvir inhibits a phosphoprotein involved in viral replication, assembly, and
secretion; sofosbuvir acts as an RNA chain terminator
B. SE and drug interactions: few side effects- fatigue & HA; Pgp-inducers will decrease
plasma concentration
● Cirrhosis = irreversible, inflammatory, fibrotic liver disease
1. Causes: Hep B & C, ETOH abuse, idiopathic, nonalcoholic steatohepatitis (NASH),
autoimmune disorders, hereditary metabolic disorders, prolonged exposure to drugs or
toxins, hepatic venous outflow obstruction (R heart failure).
2. Manifestations: Liver inflammation � Liver necrosis � Liver fibrosis and scaring �
Portal hypertension
A. Inflammation � pain, fever, N/V, anorexia, fatigue
B. Necrosis � Liver failure � Hepatic encephalopathy � Hepatic coma � Death
⮚ Jaundice and hepatobiliary mechanisms symptoms
⮚ Decreased hormone metabolism, Increased androgens and estrogens (gynecomastia,
loss of body hair, menstrual dysfunction, spider angiomas, palmar erythema),
Increased ADH and aldosterone (Edema)
⮚ Decreased metabolism of proteins, carbs, and fats (hypoglycemia), Decreased
plasma proteins (ascites and edema)
C. Portal hypertension � Ascites, edema, splenomegaly, varices
Diabetes
● Actions of Insulin
● Effects of Glucagon and Amylin
1. Glucagon – Acts in liver to increase blood glucose concentration by stimulating
glycogenolysis; in muscle by stimulating gluconeogenesis; and in adipose tissue by
stimulating lipolysis. Antagonistic to insulin
2. Amylin – Co-secreted w/ insulin. Regulates blood glucose concentration by delaying
gastric emptying and suppressing glucagon secretion after meals. Satiety affect (feel full),
(overall antihyperglycemic)
● Insulin Receptor Sensitivity = Affected by age, weight, abdominal fat (adipose cells release hormones
and cytokines that decrease sensitivity), and physical activity. Insulin resistance implicated in HTN, heart
disease, diabetes type 2.
1. Increase Sensitivity by – weight loss and exercise (cardio and go to the gym!)
● Normal Blood Glucose Values
1. Non-diabetic � 70-110; (<140 for post prandial (after meals))
2. Diabetic � 90-130; (<180 for post prandial; want higher value b/c they could bottom out
& die)
3. Diagnosis Criteria for Diabetes
A. HbA1c >/= 6.5% OR
B. Fasting blood glucose >/= 126 mg/dl (fasting for 8hrs) OR
C. 2-hr plasma glucose >/= 200 mg/dl during oral glucose tolerance test (OGTT) (they
prep you for this by making you drink syrup) OR
D. Individual w/ class symptoms of hyperglycemia or hyperglycemic crisis, a random
plasma glucose >/= 200 mg/dl
E. INCREASED RISK (pre-diabetes) – fasting blood glucose of 100-125mg/dl, 2hr
plasma glucose 140-199mg/dl during OGTT, or HbA1c 5.7-6.4%
● HgbA1C (Glycosylated Hemoglobin) = measures 3 month average blood glucose. The
normal range is 4.9-5.2%.
● Type 1 Diabetes Mellitus = most common pediatric chronic disease, 5% of diabetes cases
1. Pathophysiology – autoimmune: slowly progressive T-cell mediated destruction of
pancreatic beta cells. Combo of genetic predisposition and environmental factors (drugs,
foods, viruses; usually environmental factors are a trigger)
A. Once 80-90% beta cells destroyed, hyperglycemia occurs.
B. Insulin usually suppresses secretion of glucagon. Less insulin � increased glucagon
secretion. Glucagon will further increase blood glucose.
2. Manifestations – Polydipsia (excess blood glucose osmotically pull water from cell),
polyuria (hyperglycemia acts as osmotic diuretic-glycosuria), polyphagia (depletion of
cellular stores of carbs, fats, proteins), weight loss (fluid loss & loss of body tissue from
fat and protein), fatigue (poor use of food products), recurrent infections (growth of
microorganisms stimulated by high blood glucose), other complications from long-term
hyperglycemia.
give insulin to type 1. PT are skinny
● Types of Insulin = All do same thing, differ in onset, peak, and duration
Type of Insulin
Peak
Onse
Duratio
Exa
t
n
mple
s
Ultrashort-acting
<15
min
12hrs
~3-4hrs
Short-acting
0.51hr
23hrs
3-6hrs
Intermediateacting
12hrs
49hrs
Long-acting
24hrs
No/
mini
mal
peak
Extra info
Lisp
ro,
Aspa
rt
Reg
ular
Typically,
dosed w/
food intake
~16hrs
NPH
2024hrs
Deti
mir,
Glar
gine
Usually
administered
BID.
Morning and
evening
Typically
injected
during the
evening
Typically,
dosed w/
food intake
1. Premixed Insulins – 75/25 (75% NPH, 25% Lispro); 70/30 or 50/50 (70 NPH, 30 Regular)
● Type 2 Diabetes Mellitus
1. Risk Factors – Age, obesity, HTN, physical inactivity, family history
2. Pathophysiology - >60 genes contribute to development. Combo of genetic predisposition
and environment
A. Basic pathophysiologic mechanisms: insulin resistance and decreased insulin secretion
by beta cells.
B. Metabolic abnormalities are insulin resistance, increased glucose production in liver,
and abnormal secretion of insulin by beta cells.
C. Relative not absolute insulin deficiency. Typically diagnosed in adulthood.
D. Beta cell dysfunction could be from genetics, glucotoxicity, lipotoxicity, beta cell
exhaustion.
● Drugs for Type 2 DM “cheat sheet”
Class
Prototype
MOA
Effects
Other Important
Drug
Info
Biguanides
1st line drug
Metformin
(Glucophage)
Incompletely
understood
-Decrease hepatic
glucose
production
-First-line drug for
most patients,
-Increase insulin
sensitivity
Sulfonylureas
Meglitinides
Glipizide,
Glyburide
Binds to receptors
on surface of beta
cells
-Increase insulin
release
Repaglinide
(Prandin)
Binds to receptors
on surface of beta
cells (like
sulfonylureas, but
weaker binding)
-Increase insulin
release
Alpha-glucosidase
breaks down
starches and
disaccharides to
glucose in the gut.
By inhibiting this
enzyme, the rate of
digestion of
carbohydrates is
slowed, and the
spike in blood
glucose after a meal
is lowered
Activates
peroxisome
proliferatoractivated receptors
(PPARs), which will
increase the storage
of free fatty acids
(thus decreased in
-Reduces
postprandial (after
meal)
hyperglycemia
Alpha- glucosidase Acarbose
(Precose)
Inhibitors
Thiazolidinediones Pioglitazone
(Actos);
(TZDs)
Rosiglitazone
(Avandia)
-Improved
glucose
sensitivity/increas
ed glucose intake
especially those who
are obese
-Does NOT cause
hypoglycemia
-CI in patients with
renal insufficiency
and liver disease
-DOES have the
potential to cause
hypoglycemia
-CI with severe liver
or kidney disease
-DOES have the
potential to cause
hypoglycemia, but
less risk than
sulfonylureas
-Take 30 minutes
before each meal
-Take with first bite
of meal
-Does NOT cause
hypoglycemia
-CI in patients with
bowel disease (IBD,
colonic ulceration)
-CI in severe liver
disease
DPP-4 Inhibitors
Sitagliptin
(Januvia)
GLP-1 Receptor
Agonists
Exenatide
(Byetta);
liraglutide
(Victoza)
SGLT-2 Inhibitors
Canagliflozin
(Invokana)
circulation). Cells
become more
dependent on
glucose for energy
Blocks action of
DPP-4
(DPP-4 breaks down
GLP-1. GLP-1
stimulates insulin
release and inhibits
glucagon release.
By blocking
breakdown, GLP-1
stays around longer)
*see picture right
Binds to GLP-1
receptors
(Acts similarly to
DDP-4 inhibitors
but more potent)
Blocks the sodiumglucose
cotransporter 2 in
the kidney. More
glucose is excreted
in the urine
-Increased insulin
release
-Decreased
glucagon release
-Slowed gastric
emptying (lower
spike in blood
glucose after
meals)
-Suppress
glucagon
-Increased insulin
release
-Promote satiety
(feelings of
fullness, so will
eat less)
-Slows gastric
emptying
-Glucose excreted
through urinedecreased blood
glucose, weight
loss
-Given by injection
-CAN cause
hypoglycemia
-Risk for UTI,
dehydration,
increased risk for
DKA
● First line drug for type 2 treatment = Metformin (Glucophage)
● Hyperosmolar Hyperglycemic Nonketotic State (HHNS) vs Diabetic Ketoacidosis
(DKA) = acute complications from hyperglycemia.
1. HHNS – Precipitated by stress (infections, surgery, worsening chronic disease like kidney disease).
Pathophysiology like DKA.
A. Pathophysiology: Insufficient insulin action causes decreased muscle and adipose
glucose uptake. Also increases hepatic gluconeogenesis and increased glucagon.
Lipolysis and ketone production prevented.
⮚ Result: increased hyperglycemia � glucosuria & osmotic diuresis.
B. Symptoms: Polyuria, polydipsia, polyphagia, dehydration, and mental changes (due to
serum osmolarity has high increase >300). No “fruity” breath.
C. Important differences (see chart): Serum glucose much higher, minimal serum/urine
ketones, acidosis is minimal.
2. DKA – Lack of insulin at multiple sites. Rapid breakdown of energy deposits
A. Symptoms: Preceded by day(s) of 3 poly’s, N/V, fatigue, abd
pain/tenderness, fruity breath, Kussmauls respirations, tachycardia,
hypotension
B. Management: Replace fluid volume, decrease blood glucose, correct glucose and
electrolyte disturbances. Continuous low insulin dose therapy and slow decline in blood
glucose to prevent hypoglycemia and cerebral edema.
C. Labs: Hyperglycemia (>250mg/dl) and Elevated K+ and low Na+ (pseudo).
●
Hypoglycemia in Diabetic Patients
= completely due to treatment of diabetes
1. Causes - Insulin-treated Pts, decreased caloric intake, skipping meals & snacks, selected
oral hypoglycemic meds, incorrect dose of meds, combo therapy, exercise or increased
physical activity w/out adequate food intake.
2. Signs and Symptoms
A. Autonomic: Palpitations, nervousness, anxiety, sweating, & hunger (not present w/
hypoglycemic unawareness. Can be masked w/ beta blockers)
B. Neuroglycopenic: Irritability, confusion, drowsiness, weakness, difficulty speaking,
unconsciousness, seizures, & coma
● Micro-vascular Complications = due to exposure of excessive levels of glucose
1. Retinopathy
A. Cause: result of microvascular changes in retina. Thickened basement membrane &
pericyte death
B. Consequences: Nonproliferative = changes to microvasculature. Proliferative = new
fragile blood vessels grow that can bleed, cloud vision, and destroy retina.
2. Neuropathy – damaged blood vessels that supply nerves from constant exposure to high
glucose
A. Cause: >60% of non-traumatic lower-limb amputations in US
B. Consequences: Impaired sensation or pain in feet & hands, slowed digestion of food in
stomach, carpal tunnel syndrome, other nerve problems. Diabetic foot ulcers
3. Nephropathy
A. Cause: Damage to capillaries of kidney, the glomerulus is most commonly affected
B. Consequences: Increased urinary albumin (ACEI prescribed)
● Macro-vascular Complications
1. Cardiovascular disease & Stroke - caused by accelerated rate of atherosclerosis.
GI Disorders
● The Process of Digestion
1. Mouth (w/ salivary glands) � Esophagus � Stomach � Small intestine (w/ liver
gallbladder, pancreas) � Large intestine � Rectum � Anus
A. Mouth
⮚ Salivary amylase released and breaks down starches/carbohydrates. (Cholinergic
STIMULATE and Atropine (anti-cholinergic) INHIBITS salivation)
B. Esophagus
⮚ Swallowing: Oral phase (voluntary), pharyngeal (involuntary), Esophageal phase
(involuntary moved by peristalsis). This phase has primary (1 gulp down) or
secondary (stuffing down a big chunk which gets forced down by peristalsis)
⮚ Upper esophageal sphincter keep air out and lower prevents regurgitation
C. Stomach
⮚ Has 3 functional areas that differ in cell thickness and glands/secretions (Fundus,
body, atrium). 3 Phases of gastric secretion. Cephalic phase (~30% stimulated by
thought, smell, taste), Gastric phase (~50-60% stimulated by stomach distension),
and Intestinal Phase (~5-10% stimulated by histamine and digested protein
moderated by duodenum by arriving chyme)
⮚ Gastric secretions stimulated by eating, gastrin (hormone), paracrine pathways
(histamine), Ach (neurotransmitters), Chemicals (EtOH, coffee, protein)
⮚ Pepsinogen � Pepsin (breaks down proteins); Intrinsic factors � help absorption of
Vit B12; Gastroferrin � absorption of iron in small intestines; SOMATOSTATIN
� inhibits secretion of these
⮚ Gastric motility: peristalsis (1-way motion of chyme in caudal direction; longitudinal
muscles)
⮚ Acid acts a bactericide against swallowed microorganisms. Converts pepsinogen to
pepsin. Vagus secretes Ach (secrete histamine which produces acid) & gastric which
produces acid
D. Small Intestine – 3 segments (Duodenum, Jejunum, Ileum)
⮚ Duodenum: pancreatic amylase (polysaccharides � disaccharides); proteins
(pancreatic enzymes activated); Pancreatic lipase (triglycerides � glycerol & fatty
acids); Bile (emulsifies fats from liver in gallbladder). Main/most absorption here
and where liver dumps its products to.
⮚ Jejunum and ileum still absorb
⮚ Motility consists of segmentation (move chyme both directions for greater mixing w/
secretions; circular) and peristalsis.
⮚ Absorption occurs through villi/microvilli (more surface area = more absorption);
“Brush border” (mucosal surface of microvilli) Enzymes (disaccharides �
monosaccharides)
⮚ “Peyer patches” – lymph nodes for immune defense
E. Large Intestine
⮚ Consists of cecum, colon, rectum, anal canal
⮚ Colonic motility: haustrations (segmentation) and propulsive mass movement
F. Sites of Absorption of Major nutrients
⮚ Duodenum (Iron, Ca+, Fats, sugars, H2O, proteins, vitamins, Mg+, Na+)
⮚ Ileum (Bile sales, Vitamin B12, Chloride)
⮚ Stomach (H2O, EtOH); Jejunum (sugars, proteins), Colon (H2O, electrolytes)
⮚ These are where majority absorbed, ex. B12 being absorbed in jejunum or water in
ileum
G. 4 Layers of GI Tract (in to out) – Mucosa (mucous/enzyme production, digestion,
absorption); submucosa (blood vessels, lymphatics, nerves); Muscularis externa
(smooth muscle can be longitudinal to push down or circular to mix, also has same as
submucosa), Serosa (enclose and support; part of peritoneum)
H. Liver
⮚ Drug & hormone metabolism (biotransformation into water-soluble forms, and
detoxification or inactivation)
⮚ Carbohydrate, protein and lipid metabolism
⮚ Synthesizes clotting factors (prothrombin, fibrinogen, multiple factors)
⮚ Bile production made by hepatocytes. Bile emulsify fats � digest.
a. Bilirubin: hemoglobin from old red blood cells become unconjugated
bilirubin. Unconjugated bilirubin linked to glucuronide � conjugated bilirubin
� bile salts. Excess unconjugated bilirubin � bilirubinemia � jaundice
b. Most bile reabsorbed into blood, returned to liver for reuse, and filtered by
kidneys. Gallbladder stores and concentrates bile between meals, also absorbs
H2O & electrolytes
I. Pancreas
⮚ Secretes hormones into blood: insulin, glucagon, somatostatin, pancreatic
polypeptides. Pancreatic enzymes into duodenum: hydrolyze proteins (proteases),
carbohydrates (amylases), and fats (lipases)
● Diseases of Gallbladder
1. Cholelithiasis (gallstones)
A. Cholestasis - gallstones obstruct ducts. Liver unable to continue processing bilirubin.
Increased bile acids in blood and skin. Ducts can rupture & damage liver sells (alkaline
phosphate released into blood)
⮚ S&S: pruritus (itching), jaundice, pale stool, dark urine
B. Acute and Chronic Cholecystitis – Inflammation caused by irritation due to
concentrated bile/gallstones.
⮚ S&S: RUQ pain, N/V, fever
● Diarrhea
1. Osmotic – non-absorbable substance in intestine draws out excess water (electrolyte
absorption is normal)
A. Causes: Pancreatic enzyme deficiency, tube feeding formulas (hypertonic), osmotic
laxative abuse, carb malabsorption
2. Secretory – Excessive mucosal secretion block absorption; produces large-volume
A. Causes: Bacterial toxins, Crohn’s (IBD) disease, non-osmotic laxative abuse, reduced
absorptive surface area caused by disease or resection, luminal (like bile acids or
laxatives) or circulating secretagogues (like various hormones, drugs, and poisons)
3. Inflammatory/Infectious – produced by infection or inflammatory condition, usually selflimiting if infections. Only give antibiotics when clearly indicated to avoid resistance.
Give antibiotics for Salmonella, shigella, campylobacter, C. Diff.
A. Enterocolitis (Colo-enteritis): inflammation of enteritis of small intestine and colitis of
colon. Intestines try to get rid of infectious agent by exudate to dilute toxins,
hypermotility, or vomiting. There is a decrease in intestinal function � food not
absorbed � osmotic (or explosive) diarrhea.
B. C. Diff: Gram + anaerobic bacterium infects bowels and releases toxins. Hand washing
(not hand sanitizer) + contact isolation
⮚ Symptoms: abdominal discomfort, nausea, fever, diarrhea (has certain smell)
⮚ Treatment: Antibiotics.
4. Motility – food is not mixed properly, digestion impaired, motility increased (too fast)
A. Causes: Resection of small intestine, IBS, laxative abuse, hyperthyroidism
5. Overall Treatment
A. Obtain stool studies to rule out bacterial infection, may need imagining of abd.
B. Restore fluid & electrolyte losses, Relieve cramping w/ antispasmodics (dicyclomine
[anticholinergic]). Reduce passage of unformed stools
C. 2 major groups of antidiarrheals to reduce motility
⮚ Specific antidiarrheal drugs – bismuth subsalicylate (Pepto-Bismol)
⮚ Nonspecific – opioids (diphenoxylate/atropine NOT in C diff or children!!!)
● Irritable Bowel Syndrome (IBS) & Irritable Bowel Disease (IBD)
1. IBS – most common GI disorder, no known cause. Characterized by abd pain
A. Cause: No known cause
B. S&S: crampy abd pain, associated w/ diarrhea, constipation or both for 12
weeks over past year. Must have at least 2 of following: pain relieved by
defecation, onset associated w/ change in frequency of stool, onset of pain
occurred in associated w/ a change in stool consistency.
C. Treatments:
⮚ Drugs: Non-specific = antispasmodics, bulk-forming agents, anti-diarrheal but no
good evidence that it works better than placebo. Tricyclic antidepressants (reduce
abd pain).
⮚ IBS-specific = Alosetron (Zofran) for IBS-D, a 5-HT3 antagonist that decreases
motility. Lubiprostone for IBS-C, increases chloride-rich fluid secretion, softening
stool, increasing motility.
⮚ Other: Avoid large meals, increase dietary fluid & fiber to reduce constipation,
encourage Pt to keep food log for triggers and allergies (gluten or FODMAP
(Fermentable Oligo-, Di-, Mono-saccharides And Polyols))
2. IBD – DIFFERENT than IBS (has causes). Has 2 forms Ulcerative Colitis (UC) &
Crohn’s
A. Causes: EXAGGERATED immune response (diet, microbiota, breach of intestinal
barrier, genetics). For Crohn it is triggered by cell-mediated immune response
(autoimmune, type IV) and affects large and small intestine.
B. S&S:
⮚ UC: inflammation of mucosa & submucosa of colon & rectum. Ulcerations cause
bleeding, cramping, pain, urge to defecate. Intermittent periods of remission &
exacerbation. Most common in rectum & sigmoid colon
⮚ Crohn’s Disease: inflammation of terminal ileum/colon. “Skip lesions” can occur
and diarrhea is most common symptom.
C. Treatment
⮚ 5-Aminosalicylates: Sulfasalazine (Azulfidine) reduces inflammation and suppresses
prostaglandin synthesis & migration of inflammatory cells. Most effective against
acute episodes of mild-moderate UC.
a. SE: nausea, fever, rash, arthralgias (joint pain)
⮚ Glucocorticoids: Dexamethasone, anti-inflammatory effects for mild-moderate
Crohn that involves ileum and ascending colon
a. SE: adrenal suppression, osteoporosis, increased susceptibility to infection
⮚ Immunosuppressants: Azathioprine + Mercaptopurine, Cyclosporine, Methotrexate
used for long-term therapy in UC and Crohn’s. Drugs can take 6 months to take
effect. AE: pancreatitis and neutropenia
⮚ Immunomodulators: Infliximab (Remicade). For moderate-severe Crohn’s and UC to
induce remission.
a. Serious SE: infections, infusion reactions
⮚ Antibiotics: Metronidazole (Flagyl), ciprofloxacin (Cipro), Rifamixin (nonabsorbable rifamycin) For Crohn’s can help control symptoms and achieve &
maintain remission. For UC largely ineffective might reduce symptoms (so pretty
much useless). AE: peripheral neuropathy
● Appendicitis, Diverticulitis, Celiac Disease,
1. Appendicitis – inflammation of appendix which projects from the cecum
A. Causes: obstruction w/ stool, tumors, or foreign bodies appendix filled w/ mucus &
swells � increased pressure w/in lumen & walls of appendix � thrombosis/occlusion of
blood vessels � appendix becomes ischemic and necrotic � pain, inflammation,
perforation (hypothesis, don’t know for sure)
B. S&S: periumbilical or RLQ pain, N/V, low grade fever, leukocytosis
C. Treatments: laparoscopic appendectomy
2. Diverticulitis – sac-like outpouchings in mucosa and submucosa, usually in sigmoid
A. Causes: Exact cause unknown
B. S&S: Inflammation
C. Treatments: High fiber diet
3. Celiac Disease – one of most common genetic/autoimmune diseases
A. Causes: Have either the variant HLA-DO2 allele or HLA-DO8 allele. Tcell mediated rxn to gluten component (type IV). Antibodies �
inflammatory rxn � loss of small intestine villi � malabsorption
B. S&S: lose weight and malnutrition
● Peptic Ulcer Disease (PUD) and GERD
1. PUD – disorders that break gut wall, develops when imbalance b/w mucosal defensive and aggressive
factors.
A. Causes: usually caused by Helicobacter pylori (H. pylori), NSAIDs, stress. NSAIDs
inhibit synthesis of prostaglandins thereby decreasing submucosal blood flow, mucous
secretion. H. pylori is MOST frequent cause, bacteria live b/w epithelial cells and
mucus barrier that protects these cells.
B. S&S: anorexia, fullness, N/V
C. Treatments: Eradicate H. pylori (antibiotics), reduce gastric acidity (antisecretory
agents), enhance mucosal defenses.
⮚ Antibiotics – MOA: eradicate H. pylori. SE: nausea, diarrhea
⮚ Antisecretory agents
a. H2 receptor antagonists – MOA: suppresses acid secretion by blocking H2
receptors on parietal cells
b. PPI – MOA: suppress acid secretion by inhibiting H+, K+, ATP-ase. Can
increase risk for fracture, pneumonia, acid rebound, and intestinal infection w/
C. diff
⮚ Mucosal Protectants – MOA: forms barrier up to 6hrs over ulcer crater that protects
against acid and pepsin. AE: constipation
⮚ Antisecretory agents that enhance mucosal defense – MOA: protects against
NSAID-induced ulcers by stimulating secretion of mucous and bicarbonate,
maintain submucosal blood flow & suppression of gastric acid secretion. AE:
diarrhea and abd pain
⮚ Antacids – MOA: react w/ gastric acid to form neutral salts of low acidity, decrease
destruction of gut wall; may also enhance mucosal protection by stimulating
production of prostaglandins. AE: constipation or diarrhea.
2. GERD (heartburn, gastric regurgitation) – problem w/ inappropriate relaxation of lower
esophageal sphincter (LES) 1-2hrs after eating. Weak/incompetent
A. Causes: vomiting, obesity, pregnancy, problem w/ LES.
B. S&S: has 2 forms, Erosive (injury) – difficulty swallowing, GI bleeding, anemia,
vomiting; Non-erosive (more common)
C. Treatment: PPIs, H2s antagonists, antacids, small meals, stay upright
● Constipation
1. Categories – Normal transit (functional, hard to get out); Slow transit (impaired motor
activity, straining); Pelvic floor dysfunction (due to muscle dysfunction)
2. Classification – Primary vs Secondary (caused by stroke, Parkinson’s, spiral cord lesions,
MS)
3. S&S – hard stools, infrequent stools, excessive straining, prolonged effort, sense of
incomplete evacuation, unsuccessful defecation; < 3 BMs per week
4. Treatments – Increase fiber, decrease consumption of highly refined food, exercise, avoid
resisting urge to go, treat underlying causes (hypothyroidism, hypokalemia, diabetes),
laxatives (3 Groups: I act rapid (2-6hrs) watery consistency for preparing for
procedures/surgery – Osmotic (high dose). Group II: 6-12hrs, semifluid stool – Osmotic
low (low dose) and stimulant. Group III, more frequently abused, 1-3 days, produce soft
formed stool for chronic constipation and prevent straining – bulk-forming, surfactant,
others
A. Osmotic Laxatives – MiraLAX, Lactulose, Magnesium hydroxide
⮚ MOA: poorly absorbed salts that draw water into intestinal lumen; fecal mass softens
and swells, wall stretches, and peristalsis is stimulated.
⮚ SE: dehydration, abd bloating, cramping, flatulence, avoid MOM in Pt w/ kidney
disease: Na retention: exacerbated HF, HTN, edema.
B. Stimulant Laxatives – Dulcolax, Senokot
⮚ MOA: stimulate intestinal motility. It increases amount of water & electrolytes w/in
the intestinal lumen by increasing secretion of water and ions into the intestine and
by reducing water and electrolyte absorption. Works w/in 6-12hrs to produce a
semifluid stool
⮚ SE: widely abused, long term use discouraged
C. Bulk Forming Laxatives – Citrucel, Metamucil
⮚ MOA: Consist of natural or semi-synthetic polysaccharides and celluloses which
swell in water (like fiber). Intestinal transit time is slowed as the fecal mass stretches
the intestinal wall peristalsis.
⮚ SE: RARE, need to take w/ full glass of juice or water
D. Surfactant Laxatives – Docusate Sodium (Colace)
⮚ MOA: Alter stool consistency by lowering surface tension, which facilitates
penetration of water into feces. Inhibit fluid absorption. Stimulate secretion of water
and electrolytes into intestinal lumen (like stimulant laxatives)
E. Other Laxatives – Amitiza, Mineral Oil, Glycerin Suppository
⮚ MOA: selective Cl channel activator. Promotes secretion of Cl-rich fluid into
intestine. Enhances motility in small intestine & colon: lubrication. Osmotic agent
that softens & lubricates hardened, impacted feces.
⮚ SE: anal leakage, and deposition of mineral oil in liver.
● Emesis and Motion Sickness
1. Emesis
A. Causes: medulla oblongata (vomit center) senses chemicals in blood or peripherally
Vagus nerve (a lot in colon)
B. Triggered by
⮚ Direct-acting stimuli: signals from cerebral cortex (fear), signals from sensory
organs (upsetting sights, noxious odor, pain), inner ear vestibule
⮚ Indirect-acting stimuli: involves the CTZ (chemoreceptor trigger zone) which is
activated from the stomach, intestines OR from medications (opioids, chemo drugs)
C. Treatments: Antiemetic drugs, they suppresses N&V which originates in medulla
oblongata/Vagus nerve
⮚ Serotonin receptor antagonists – MOA: blocks 5HT3-receptors located in the CTZ
and on afferent vagal neurons in upper GI tract. SE: HA, diarrhea, dizziness, QT
prolongation. Highly effective (ex. Zofran)
⮚ Dopamine receptor antagonists – MOA: suppresses nausea through blockade of
dopamine receptors in the CTZ. SE: hypotension, sedation, respiratory depression
(ex. Prochlorperazine (Phenergan), Metoclopramide (Reglan))
⮚ Substance P/neurokinin1 receptor antagonists – MOA: blocks neurokinin1 type
receptors in the CTZ (prevents postop N/V and CINV). SE: well tolerated
⮚ Cannabinoid agonists – MOA: unclear but activates cannabinoid receptors. SE:
Potential for abuse & psychotomimetic effect. Anorexia/wasting in AIDS
⮚ Antiemetics are more effective in preventing CINV than in suppressing CINV in
progress. Give before chemotherapy drugs. Monotherapy and combo therapy may be
needed.
2. Hyperemesis gravidarum – N/V of Pregnancy
A. SE: dehydration, ketonuria, hypokalemia, and loss of 5% or more of body weight
B. Treatments: Ginger, First-line therapy is Antihistamine (doxylamine) + Vitamin B6.
Other drugs like dopamine/serotonin antagonists.
3. Motion sickness – triggered from signals to inner ear vestibule
A. Treatments:
⮚ Muscarinic Antagonists, Scopolamine, SE: dry mouth, blurred vision, drowsiness.
⮚ Antihistamines: Considered anticholinergics; block receptors for Ach and histamine.
SE: sedation (H1 receptor blocking), dry mouth, blurred vision, urinary retention,
constipation (muscarinic blocking) (ex. Dimenhydrinate, meclizine, cyclizine)
● GI Bleeding
1. Hematemesis – bloody vomit, characterized by frank, bright red blood = above stomach,
or dark, grainy digested blood “coffee-ground” = stomach
2. Melena – black, tarry, sticky, foul-smelling stool containing partly digested blood. Need
to distinguish from stool containing iron supplements, black berries or Pepto-Bismol ask if
they had any of these since it looks similar.
3. Hematochezia – fresh, bright red blood passed from rectum. Over strained
4. Occult Blood – trace amounts of blood in normal looking stools, detected w/ guaiac test,
usually SLOW or chronic blood loss (not obvious) (a small CULT hiding in stool)
5. Upper GI Bleeding (UGIB) – bleeding varicose veins in esophagus, peptic ulcers, Mallory
Weiss tear (tear in mucosal layer at junction of esophagus and stomach)
6. Lower GI Bleeding (LGIB) – bleeding from jejunum, ileum, colon, rectum. Caused by
polyps, diverticulitis, inflammatory disease, cancer, hemorrhoids
● Bowel Obstruction
1. Intestinal Obstruction condition that prevents normal flow of chyme through intestine
A. Categorized/Causes: SIMPLE: mechanical blockage of lumen by lesion, most common
or FUNCTIONAL (paralytic): failure of intestinal motility often after abd surgery.
B. Extra info: Vomiting � fluid and electrolyte loss; fluids move into intestinal contents;
gas accumulates; distension of bowel; compartment syndrome � ischemia, necrosis can
lead to bowel PERFORATION; anaerobic bacteria produce endotoxin � toxemia
C. S&S: Cardinal signs: crampy, colicky pain followed by vomiting, distension; If
strangulation � pain becomes more constant & severe; If partial obstruction � diarrhea
&/or constipation are present. Early obstruction has “tinkly” bowel sounds and late has
ABSENT sounds.
D. Treatments: decompression (NGT), immediate surgery PRN, antisecretory agents
● Feeding Tubes Types
1. NG (short term, NG drainage), Nasoduodenal/Nasojejunal, Orogastric, Percutaneous
endoscopic (insert here)stomy (need surgery for), Gastric (long term, gastric drainage),
Gastrojejunal (drainage & feeding), Jejunal, Parenteral nutrition (IV)
2. Ileostomy/colostomy = either ileum or colon is out of abd wall
Endocrine Disorders
● Functions of the Endocrine System
1. Differentiation of reproductive/central nervous systems in the fetus
2. Stimulates growth & development
3. Coordinates male & female reproductive systems
4. Maintains an optimal internal environment throughout life
5. Initiation of corrective & adaptive responses when EMERGENCY arises
● Characteristics of Hormones
1. Compound that exert various effects/functions in different tissues, or a single function can
be regulated by different compounds (a lot of overlap = a lot of backup, just in case)
2. Classes of Hormones
A. Amines/amino acids
B. Steroids (made from cholesterol)
C. Eicosanoids (made from fatty acids; prostaglandins, prostacyclin, leukotrienes and
thromboxane)
D. Peptides, polypeptides, proteins, and glycoproteins
3. Secretions can be endocrine (hormone travels through blood stream to distant target cell),
Paracrine (hormone travels to nearby target cell, local), or Autocrine (hormone effecting
itself)
4. Hormones have specific rates & rhythms of secretion
A. Circadian or pulsatile & cyclic (feedback loops)
5. After only TARGET cells w/ specific receptors, release determined by chemicals (blood
sugar levels), endocrine factors (one gland controlling another), neural control, mixed
6. Hormone transport – water soluble hormones: unbound (free). Binds to cell-surface
receptors and cannot diffuse across the cell membrane (first and second messenger).
ONLY FREE hormones can signal a target cell. Lipid soluble hormones: bound to carrier
or transport protein half-life longer.
7. Degradation – may be excreted by the kidneys, destroyed in liver and excreted in bile
(steroid hormones, T4 to T3), destroyed by enzymes at receptor (epinephrine, dopamine),
may be take up by cells and destroyed (peptide hormones)
8. Hormone action – more receptors on cell � more sensitive; up-regulation: low conc. of
hormone � increase # of receptors. Down-regulation: high conc. Of hormones � decrease
# of receptors
● Feedback Loop = Positive on top, Negative on Bottom. (For negative when D releases 4 to cause less A, 4
can also possibly affect B)
● Hypothalamus-Pituitary (HP) Axis
1. The hypothalamus either release hormones that enters portal circulation � to anterior
pituitary endocrine cells w/ receptors OR sends neuronal projections to posterior
pituitary.
2. Anterior Pituitary (AP) – hypothalamus release (neuro)hormones � portal circulation �
AP and releases hormones � systemic circulation � cells w/ receptors. (Releases GH,
Corticotropin (adrenocorticotropic hormone, ACTH), Thyrotropin (thyroid-stimulating
hormone TSH, Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Prolactin
3. Posterior Pituitary (PP) – hypothalamus release projections � PP stores/releases
hormones � systemic circulation � cells w/ receptors. (PP gets hormones from the
hypothalamus to store and release vs AP which makes its own) (Releases oxytocin &
ADH) (Think about storing PP and projecting it)
4. The hypothalamus detects the state of the body: temp, blood osmolarity, nutrients,
hormones levels, inflammatory mediators in blood, emotions, pain
5. Regulating factors: Gonadotropin releasing hormone (GnRH), Growth hormone (GH-RH),
Thyrotropin (TRH), Prolactin (PRF), Corticotropin (CRH); inhibitory: Somatostatin,
Dopamine
● 3 Categories of Hormone Level Dysfunction (3 � 1, top – down)
1. Tertiary – abnormality in the hypothalamus
2. Secondary – abnormality in the anterior pituitary
3. Primary – abnormality in the peripheral gland
● Thyroid/Parathyroid Disorders = Thyroid: responsible for metabolism, cardiac function, growth &
development. Regulated by negative feedback loop (TRH � T3/TH) so as TH levels rise � inhibition of TSH &
TRH. T3 active form, T4 mostly inactive. Parathyroid: has PTH regulates serum calcium (phosphate) by
activating osteoclasts in bone and upregulates enzyme so Vitamin D will increase gut absorption of
Ca/phosphate. Also, parathyroid acts on kidney to increase Ca reabsorption and inhibit reabsorption of
phosphate (more ionized Ca)
1. Hypothyroidism – high TSH, low T4 & T3
A. Causes: Decreased circulating TH, Thyroid insufficiency due to lack of I-, T3/T4 not
made, no negative feedback, and TRH & TSH continue to be made � goiter
B. S&S: Hair loss, constipation, cold intolerance, puffy face, bradycardia, low energy,
weight gain, Goiter (enlarged thyroid gland, too much TSH)
C. Treatment: Replace T3/T4 w/ synthetic version Synthroid (levothyroxine [T4]) daily
PO, preferably in morning (insomnia) on empty stomach (decreased absorption if you
have), takes 1 month to take effect
2. Hyperthyroidism – low TSH, high T4 & T3, (for labs would test all these + TSIs)
A. Causes: Increased circulating TH, suppressed TSH
B. S&S: Thin hair, hyperreflexia, tremor, tachycardia, Goiter (TSI), exophthalmos (would
get last 2 if you have Grave’s disease)
C. Treatment: Decrease production of TH by surgical removal of gland, destruction of
thyroid tissue w/ radioactive iodine, or suppress TH synthesis w/ anti-thyroid drugs
(Methimazole or Propylthiouracil (PTU))
⮚ Methimazole is safer & more convenient than PTU but AVOID 1st trimester of
pregnancy. Both MOA is block synthesis of TH & SE of agranulocytosis
⮚ PTU should ONLY be given 1st trimester of pregnancy, SE: agranulocytosis
(lowered WBC count), & liver failure (that’s why you don’t use this shit)
3. Hypoparathyroidism
A. Causes: Damage to gland during thyroid surgery, or hereditary. Deficient PTH
secretion � low serum Ca+, high Phosphate.
B. S&S: hypocalcemia (numbness & tingling, twitching, skeletal muscle cramps,
hyperactive reflexes, carpopedal spasms, laryngeal spasms, tetany, hypotension,
fractures, brittle hair, nails, and ECG changes: prolonged ST, QT interval changes)
C. Treatment: Correct Ca
4. Hyperparathyroidism
A. Causes: 80% of primary cases due to adenomas. Excess PTH secretion � elevated
serum Ca, low Phosphate
B. S&S: hyperCa+, hypophosphatemia, frequent fractures, hypercalciuria
C. Treatment: Remove adenoma, Ca lowering drugs
● Adrenal Disorders = Adrenal gland: AP send ACTH to adrenals to secrete glucocorticoids (cortisol) or
mineralocorticoids (Aldosterone). Cortisol increases blood glucose, promotes protein breakdown and fat
breakdown, influences level of awareness and sleep, response to stress (SNS response) and suppresses
immunity & inflammation.
1. Addison’s Disease (Adrenal Insufficiency) – inadequate cortisol levels w/ elevated
ACTH (loss of negative feedback)
A. Causes: autoimmune mechanism that destroys adrenal cortical cells
B. S&S: skin hyperpigmentation, vomiting, diarrhea, hypotension
C. Treatments: Hydrocortisone (drug of choice), glucocorticoid & mineralocorticoid
replacement therapy
2. Adrenal Crisis (Addisonian Crisis/Acute adrenal insufficiency)
A. Causes: undiagnosed Addison’s, trauma, etc
B. S&S: sudden onset – hypotension, dehydration, weakness, lethargy, N/V
C. Treatments: glucocorticoids/mineralocorticoids, rapid replacement of fluid, salt
⮚ Hydrocortisone – glucocorticoid, identical to that of cortisol, binds to GRs and
MRs. No SE when given proper dose
⮚ Fludrocortisone – Only mineralocorticoid available. SE: salt & water retention in
excess, HTN, edema, hypokalemia
3. Cushing’s Syndrome/Disease – excess cortisol and ACTH secretion
A. Causes: pituitary adenoma, ectopic nonpituitary tumor
B. S&S: weight gain (buffalo hump, moon face), hyperglycemia, muscle weakness,
fractures, growth retardation, skin changes, HTN, increased hair growth
C. Treatments: Meds, radiation, surgery to remove diseased adrenal gland
● Growth Disorders = Hypothalamus secretes GRH � AP � GH (stimulated by hypoglycemia, fasting,
starvation, stress, exercise, heat); Somatostatin � inhibits AP. (GH inhibited by increased glucose levels, free
fatty acid release, obesity, cortisol)
1. Growth Hormone Deficiency
A. Idiopathic GH deficiency: lacks hypothalamic GHRH
B. Pituitary tumors, agenesis of the pituitary: lack GH
C. Laron-type dwarfism: Abnormal GH receptor
2. Growth Hormone Excess
A. Gigantism: caused by adenomas, happens before puberty (epiphyseal growth plates are
open during childhood)
B. Acromegaly: growth of bone (thickening), skin, muscles, heart, liver, and GI.
Happens after puberty. Treatment: Lanreotide/Octreotide (analogues of
somatostatin)
● ADH Disorders = diseases of Posterior Pituitary
1. SIADH – high levels of ADH
A. Causes: meds, various cancers, tumors, trauma, infections
B. S&S: thirst, vomiting, confusion, Cardinal features: renal water retention, dilutional
hyponatremia
C. Treatment: fluid restriction, Tolvaptan (ADH receptor 2 antagonist)
2. DI – low levels of ADH
A. Causes: Neurogenic brain tumors, aneurysms, infections, head injuries. Nephrogenic:
inadequate response of renal tubules to ADH, due to kidney disease, medications
B. S&S: cannot concentrate urine! Polyuria, thirst
C. Treatment: Reverse underlying cause, may need to give ADH (desmopressin) SE risk
of water intoxication.