PHCL III

Skin, GI

Name the layers of the skin deep to superficial, naming the layers of the epidermis as well.

Hypodermis, dermis, epidermis (Stratum basale, spinosum, granulosum, corneum)

Glands, nerve endings, and hair follicles reside in which layer of the skin.

Dermis

The _____ layer of the epidermis is made up of a lot of keratin, and dead karatinocytes.

Stratum corneum

If you have a wound, the stem cells that replace the epidermis for healing come from?

hair follicle

(True/False) In healthy skin, TLR4 stains only show up in the basal layer of epidermis.

True

This disease is caused by uncontrolled keratinocyte proliferation and dysfunctional keratinization due to sustained inflammation. It can be triggered by trauma, stress, or pathogens and has autoimmune traits.

Psoriasis

Methotrexate works to treat psoriasis by doing what?

Dihydrofolate reductase inhibition to block purine synthesis, this leads to lymphocyte apoptosis

Methotrexate is a psoriasis treatment, and also a…

cancer treatment

Retinoid works to treat psoriasis and as a skin treatment by…

increasing skin cell turnover

Acetretin works to treat psoriasis by…

decreasing the speed of keratinocyte turnover

____ is a psoriasis treatment that can cause increased cholesterol and hepatotoxicity. _____ should be avoided during and after treatment due to a long elimination time.

Acetretin, pregnancy

Apremilast works by…

inhibiting PDE4, which leads to increased cAMP

Which two topical psoriasis treatments work by slowing keratinocyte proliferation?

Calcipotriene and Calitriol

What type of medications target the inflammatory cytokines that play a role in psoriasis?

monoclonal antibodies

Atopic dermatitis differs from psoriasis in that…

it is not chronic, is more common in children, and is characterized by red and inflamed skin, rather than scales

(True/False) A blackhead is a different color than a whitehead because it is dirt in a pore, while a whitehead is a buildup of oil.

False

Retinoic acid is used to treat acne because it…

increases epithelial cell turnover and decreases keratinocyte adhesion

Adalpine…

works similarly as retinoic acid, but is safer in the sun and can be combined with benzoyl peroxide

A patient comes into the clinic with acne that is clearly caused by bacterial overgrowth. She works outdoors in the sun four days a week. She also is currently trying to get pregnant. Which of the following would you probably prescribe?

Adalpine and benzoyl peroxide

This treatment is thought to be effective as an active treatment by reducing sebaceous gland size and function. It is NOT recommended for pregnant women.

Isotreninoin

Benzoyl peroxide works by…

penetrating the skin, killing bacteria, clearing debris

Topical corticosteroids can also be used to serve as anti-inflammatory agents for treatment. Besides the different absorption rates in different areas, what should be taken into account?

Large doses can inhibit the HPA axis and simulate Cushing’s syndrome, and topical use can even lead to skin atrophy over time

What is an uncommon treatment for inflammatory diseases that is used when corticosteroids are not effective?

Tar compounds

What is another common method of drug delivery? Fentanyl, nictonine, etc can be delivered this way.

Dermal patch

What is the upside of a transdermal patch?

The dosing is consistent over time, it bypasses the GI route, and allows for lower doses

A scopolamine patch is used to treat…

nausea

A clonidine patch is used to treat…

high blood pressure

A patient comes in after a trip. He states he fell asleep in the sun and suffered a blistering sunburn. You schedule a yearly dermatology exam for the foreseeable future, why?

A single blistering sunburn can double the chances of melanoma later in life

UVA exposure increases the chance of melanoma. Why?

Increasing the generation of ROS

UVB exposure increases the chance of melanoma. Why?

Through the excitation of molecules, leading to the creation of pyrimidine dimers

Exposure to which of the following types of UV light is capable of causing initiation, promotion, and progression of cancer?

UVB

What is the associated issue in the initiation step of skin cancer?

DNA photoproducts causing RAS and TP53 mutations

What is the associated issue in the promotion step of skin cancer?

Signaling pathways transactivate AP-1 and stimulate COX2 expression, which leads to benign papilloma formation

What is the associated issue in the progression step of skin cancer?

A constitutive AP-1 and COX2 expression, leading to genetic instability which causes malignant conversion and metastasis

What is the best way to avoid skin cancer?

Sunscreen

Basal cell carcinoma is characterized by ___ in appearance, and is treated by….

being a pink pearly bump, surgery, topical sensitizers, phototherapy, radiotherapy, and in advanced cases systemic treatment

A patient that has worked in construction comes into the clinic complaining of a pink pearly bump on his arm that he initially thought was acne. It has not gone away in weeks. You ask if he wears long sleeves or sunscreens, and he states he only applies sunscreen before leaving for work. What is your initial diagnosis, and what would be the treatment plan?

Basal cell carcinoma, surgical removal followed by treatment immune sensitizers and phototherapy. Consider radiation.

A patient comes into the clinic. She has worked as an outdoor swim instructor for 5 years. She comes in complaining of a scaly bump on her hand that has not healed for two weeks. She has tried peeling the scale, but it only comes back, and neosporin and anti-inflammatories have not helped. She states she applies sunscreen on her arms and face, reapplying after two hours. However, she does not apply any to her hands. What is your initial diagnosis, and what would be the treatment plan?

Squamous cell carcinoma, surgical removal followed by treatment immune sensitizers and phototherapy. Consider radiation and cryotherapy

A patient comes into the clinic complaining of a new raised brown bump on her arm. She is a gardener, and often works in the sun. She states she does commonly forget to apply sunscreen, and she works for hours at a time outside. The bump appeared a week ago, what is your initial diagnosis and what would be the treatment plan?

Melanoma, surgery followed by chemotherapy, targeted therapy, or immunotherapy

A patient comes into the clinic complaining of substernal burning after eating meals. He mentions that antacids help after reflux, but moving around aggravates the symptoms. You do a barium swallow study, and you can visualize a bulge where the LES typically is. This patient has what disease, and what is causing it?

GERD, hiatal hernia

A hiatal hernia is caused by…

a weak LES and therefore slippage of the lower stomach above the diaphragm.

What can lead to a hiatal hernia?

A large esophageal hiatus, injury/trauma to abdomen, obesity, intense/persistnet pressure on surrounding muscle of hiatus

Which of the following hiatal hernia subtypes is most dangerous?

paraesophageal

Ok. You have diagnosed a patient with GERD due to a sliding hiatal hernia. He mentions that this is common in his family, and he has been struggling with the reflux for years now. If you do further investigation with an endoscopy, what may you find?

erosive esophagitis, barrett’s esophagus, peptic stricture, esophageal cancer

Your patient with GERD due to a small sliding hiatal hernia does not present with any esophageal epithelium remodeling. He presents with intense GERD symptoms everyday. Would prescribing an antacid be recommended? Why?

No, antacids are meant to be used to mitigate mild GERD symptoms that occur less than once a week

NOTE: Here are all the adverse effects of each type of antacid

Aluminum containing
Retention in CRF leading to neurotoxicity/anemia
Hypophosphatemia
Constipation

Magnesium containing
Diarrhea
Hypermagnesemia (w/ renal disease)

Calcium contaitng
Hypercalcemia
Alkalosis
Acute renal injury
Constipation

Sodium containing
Volume overload in susceptible patients
Hypertension exacerbation

ok

A patient with mild GERD comes into the clinic. She complains of symptoms about once a week or less after meals. She is a dialysis patient due to renal failure. Which type of antacid would you prescribe.

Sodium containing

A patient with mild GERD comes into the clinic. He complains of symptoms about once a week or less after meals. He suffers from hypertenstion and edema due to CHF. His bloodwork shows his magnesium and calcium are typically elevated. Which type of antacid would you prescribe.

Aluminum containing

A patient with mild GERD comes into the clinic. She complains of symptoms about once a week or less after meals. She is a an older patient with a history of SBO, CHF, and her labs show her magnesium is typically low. Which type of antacid would you prescribe.

Magnesium containing

A patient with mild GERD comes into the clinic. She complains of symptoms about once a week or less after meals. He has history of fluid retention, hypertension, hypocalcemia, and hypermagnesemia. Which type of antacid would you prescribe.

Calcium containing

You have medication A and B. Drug A has a 50% analgesic effect at a 0.01 dose, but Drug B has a 20% analgesic effect at 0.1 dose. Which of the following is a more potent drug? (Which would you prescribe to a patient with extreme chronic pain?)

Drug A

Which of the following does NOT stimulate parietal cell secretion?

epinephrine

What is the mechanism of parietal cell stimulation for histamine?

H2 receptor binding activates adenyl cyclase, increasing cAMP, stimulating proton pump

What is the mechanism of parietal cell stimulation for gastrin?

CCK2 receptor binding increases intracellular Ca2+ conc. which stimulates proton pump

What is the mechanism of parietal cell stimulation for acetylcholine?

m3ACh receptor binding increases intracellular Ca2+ conc. which stimulates proton pump

NOTE:

Here are the H2RAs!

Cimetidine
Famoridine
Nizatidine

Ranitidine is NOT used anymore

-idine means H2 receptor antagonist

Act by blocking histamine binding to H2 on parietal cell and blocking acid release via histamine pathway. Slower onset but longer duration than antacids. It inhibits postprandial and nocturnal acid secretion!!!

Contraindications: CYP450 drugs like
warfarin
diazepam
pheytoin
quinidine
carbamezapine
theophyline
imipramine

ok

A patient comes to the clinic and after an initial history, barium swallow study, and an endoscopy it is determined he suffers from GERD do to a mild sliding hiatal hernia. His symptoms occur nearly every day of the week, bloodwork shows hypercalcemia, and he is currently taking warfarin. Which of the following would be best to prescribe?

Nizatidine

Why was the H2RA ranitidine recalled and removed from sale to the public?

Cancerous NDMA was found to increase in concentrations in ranitidine products when they were stored at higher than room temp.

A patient comes to the clinic and after an initial history, barium swallow study, and an endoscopy it is determined he suffers from erosive esophagitis due to GERD due to a mild sliding hiatal hernia. His symptoms occur nearly every day of the week, bloodwork shows hypercalcemia, and he is currently taking warfarin. Which of the following would be best to prescribe?

Omeprazole

NOTE:

Here are the PPIs!!

Omeprazole
Esomeprazole
Lansoprazole
Rabeprazole
Pantoprazole
Omeprazole/Na Bicarb
Dexlansoprazole

-prazole means proton pump inhibitor

Works by covalently binding to proton pump and therefore inhibiting acid release via ANY pathway as histamine, gastrin, and ACh can bind to receptors on on parietal cell but proton pump is still not going to pump acid into stomach lumen.

BECAUSE PPI binds covalently to the pump, new pumps must be transcribed in order for cell to begin pumping acid again = long lasting effect

Does lead to increased rate of healing of erosive esophagitis and peptic ulcers

ok

What is the relationship between stress and cortisol release? (does stress stimulate cortisol release or not?)

Stress stimulates the release of cortisol, increasing conc. in blood from ~700nM up to ~1100nM.

Describe the steps leading to cortisol release starting from a stressor.

Stress, hippocampus, hypothalamus releases CRH, CRH acts on ant. pituitary, ant. pituitary releases ACTH, ACTH acts on adrenal cortex, adrenal cortex releases cortisol which inhibits hypothalamic CRH release and pituitary ACTH release.

Cortisol is synthesized in?

zona fasciculata

Aldosterone is synthesized where?

zona glomerulosa

Androgens are synthesized where?

zona reticularis

What are the four metabolic effects of glucocorticoids?

increased gluconeogenesis, inhibit glucose uptake in muscle and adipose tissue, increase protein/lipid catabolism, increase bone loss

Are glucocorticoids immunosuppressive or immunostimulatory?

suppressive

When exposed to stress, do men or women have a more acute cortisol spike?

men

Cortisol concentration (falls/spikes) during sleep, and (falls/spikes) right before waking.

falls, spikes

Melatonin concentration (falls/spikes) during sleep, and (falls/spikes) right before waking.

spikes, falls

In repeated homotypic stress with habituation, novel stress in time will lead to what type of HPA response?

acute

In repeated homotypic stress with no habituation, novel stress in time will lead to what type of HPA response?

acute

(True/False) Glucoocorticoids can increase short term memory

True

Which of the following is FALSE regarding corticosteroids?

stimulate glucose uptake in muscle and adipose tissue

A corticosteroid deficiency is called…

Addison’s disease

A patient enters the clinic presenting with fatigue, hyperpigmentation, weight loss, and muscle weakness. Upon vitals check, she presents with a BP of 92/63 and a blood glucose of 76. She begins presenting with nausea and vomiting so you admit her. Her bloodwork shows she has extreme hyponatremia and mild hyperkalemia. You diagnose her with what? Should you immediately put her on fluids? Are fludrocortisone and oral hydrocortisone appropriate treatments?

Addison’s disease, yes, yes.

A patient comes into the clinic due to a cut that won’t heal and new onset fatigue and memory loss. Upon vitals check, he presents with a BP of 184/95 and a blood glucose of 245. His medical records also show that his last appointment with his PCP led to a glaucoma and osteoporosis diagnosis. He also presents with a moon face, and various bruises. You admit him, and diagnose him with what?

Cushing’s syndrome

The liver, gallbladder, an d pancreas are connected by?

the common bile duct

An islet of Langerhans contains what cells?

alpha, beta, delta, G, and F

Alpha cells of the pancreas secrete…

glucagon

Beta cells of the pancreas secrete…

insulin

Delta cells of the pancreas secrete…

somatostatin

Somatostatin action is?

Inhibition of secretory cells and a GH inhibitor

Gastrin action is?

stimulation of gastric acid release

Which of the following correctly orders the steps for insulin processing in pancreatic beta cells?

1. Preproinsulin is translated and simulaneously translocated.into ER lumen

2. In ER lumen, signal sequence is cleaved and proinsulin is formed. Folding occurs and disulfide bonds form between A/B segments of proinsulin.

3. Proinsulin travels to Golgi via vesicular transport

4. In trans-Golgi and immature secretory vesicle, protein is cleaved by pro protein convertases and insulin and C peptide are produced.

5. Insulin and C peptide are stored in secretory granules

6. Ca2+ influx stimulates fusion of granule with basolateral membrane and subsequent insulin release.

Insulin peptide is compromised of…?

A and B chains of preproinsulin joined by disulfide bonds

How does glucose signal insulin release in a pancreatic beta cell?

Glucose enters via GLUT2 transporter, where it is metabolized and produces ATP. The ATP influx then blocks the efflux of K+. This depolarizes the cell, opening voltage gated ion channels, and therefore allowing Ca2+ to flood in. This then stimulates the release of insulin.

Name the steps of insulin signaling in muscle and adipose tissue, ending with the 5 end results.

Insulin binds the alpha subunit of insulin TrkR. This signals beta subunit to transmit signal via auto-phosphorylation of Tyr residues in the cytoplasmic tails. Protein kinases from these then phosphorylate IRS, Shc, and other proteins. IRS and Shc phosphorylation stimulate mitogenesis, protein synthesis, glycogen synthesis, and glucose transport. Phosphorylation of other proteins (and PI3-K) stimulates GLUT4 synthesis and translocation to the plasma membrane, allowing for glucose influx. This is then metabolized and stored.

(True/False) GLUT2 is found in every cell.

False

(True/False) GLUT1 is found in all tissues

True

Which of the following glucose transporters is typically found in beta cells of the pancreas, in the liver, kidney, and gut?

GLUT2

Which of the following glucose transporters is typically found in muscle and adipose tissue?

GLUT4

Which of the following does NOT lead to an increase in blood glucose?

mineralorticoids

Does insulin increase protein synthesis in the liver?

No

Which of the following store glucose and glycogen after insulin signaling?

liver

(True/False) Insulin signaling in muscle inhibits glucose transport

false

A patient’s blood sugar is 85 mg/dL. We can assume they are in a (fasting/prandial) state and most of their glucose stores are going to (brain/SKM/liver).

fasting, brain

A patient’s blood sugar is 145 mg/dL. We can assume they are in a (fasting/prandial) state and glucose is mostly being mobilized to (brain/SKM/liver).

prandial, liver/SKM

Which of the following is characteristic of Type 1 diabetes?

insulin-dependent diabetes, selective beta cell destruction, insulin
deficiency

Which of the following is characteristic of Type 2 diabetes?

non-insulin dependent, tissue resistance to insulin, relative deficiency of insulin