Third 50

Question 1

Gastric Acid Secretion Mechanisms

Answer 1

-Parietal cell secretes it..Found in mucosal glands of the fundus and the body. Triggered by
1) Acetylcholine- M3 receptors- Ca release
2) Histamine-released by ECL- H2 receptors increased cAMP
3) Gastrin- GR on parietal cells, increased Ca. Also increases histamine synthesis and release by ECL (MOST IMPORTANT action)
Ca and cAMP activate PKinases, hence increased H/KL ATPASE

Question 2

Mastocytosis, describe, GI observations

Answer 2

Cramps and Increased mast cells in mucosa..non GI related are pruritus, urcticaria, dermatographism, rash, flush

Question 3

Gastric paresis or hypomotility

Answer 3

Hypothyroidism, uremia, DM, metabolic disturbances

Question 4

Triple test? (pregnancy)

Answer 4

1. AFP:- made by fetal liver, GI tract and yolk sac in early gestation. Maternal serum level increases with increased gestational age. Most common cause for increased levels is dating error (gestational age underestimated!!!! Other causes are neural tube defects, abdominal wall (omphalocele/gastroschisis) and multiple gestation..Downs syndrome = decreased AFP
2. Estriol:- reflect placenta and fetal function…if decreased , placental insuffiency
3. HCG:- made by trophoblastic tissue..increased levels correlate with multiple gestation, hydatidiform mole and choriocarcinoma

Question 5

Use of Nitrates and paradoxical effect..solution? Is nifedipine helpful

Answer 5

Used in stable angina..
It is a vasodilator that decreases blood pressure
However, reflex tachycardia ensues, which increases myocardial o2 demand even though they are anti ischemic drugs…Use metoprolol or beta blockers to slow AV node conduction at beta1 receptor sites

NIFEDIPINE is a peripheral CaCB and can cause reflex tachycardia! Cardioselective CCB like Verapimil or diliatezem are better!!! They slow AV nodal conduction but beta blockers more effectively blunt the tachycardic response induced by nitrates

Question 6

Name one alpha agonist and an antagonist and describe their function..do any of them cause reflex tachycardia…Describe hydralazine does it cause reflex tachycardia?

Answer 6

Agonist:- Phenylephrine, used as a vasopressor in shock cases or severe hypotension cases. Causes reflex BRADY as it is a POTENT vasoconstrictor
Antagonist:- Prazosin is a selective alpha 1..use in HTN and BPH. Peripheral vasodilator…Selective alpha blockers DO NOT cause reflex tachy as PRESYNAPTIC alpha 2 inhibition is not blocked

Question 7

Name one alpha agonist and an antagonist and describe their function..do any of them cause reflex tachycardia…Describe hydralazine does it cause reflex tachycardia?

Answer 7

Agonist:- Phenylephrine, used as a vasopressor in shock cases or severe hypotension cases. Causes reflex BRADY as it is a POTENT vasoconstrictor
Antagonist:- Prazosin is a selective alpha 1..use in HTN and BPH. Peripheral vasodilator…Selective alpha blockers DO NOT cause reflex tachy as PRESYNAPTIC alpha 2 inhibition is not blocked

Question 8

Where in respiratory tract is there ciliated mucosal epithelium..Function of Clara cells

Answer 8

NOSE to TERMINAL bronchioles lined by ciliated mucosal epitheliumn (BUT THERE ARE NO MUCOUS SECRETING CELLS WITHIN THE BRONCIOLES, EPITHELIAL CILIAL THERE DO OUTWARD CLEARANCE. SUBMUCOSAL MUCOUS AND MUCOSEROUS GLANDS FOUND IN OUTERMOST AIRWAY THROUGH BRONCHIA!!!!)
..MUCOCILIARY clearance ensures particles greater than 2 microns do NOT reach the alveoli…
They are non ciliated, found in terminal respiratory epithelium,,secrete clara cell secretory protein or CCSP which is part of surfactant, also detoxify inhaled toxins by cytP450..

Question 9

What is responsible for HIV resistance to standard protease inhibitors
What encodes for structural glycoproteins

Answer 9

Pol gene mutations which are responsible for structural HIV RT changes making it resistant to standard NNRTs or NRT
HIV env gene encodes for the viral envelope glucoproteins which mutates to ensure humoral response resistant

Question 10

Describe the structure of insulin and what drug increases insulin secretion and C peptide

Answer 10

N terminus is beta chain, then theres a C peptide and C terminus is A chain. A and B joined by disulfide bonds..C peptide cleaved from proinsulin by beta cell peptidases. bOTH ARE PACKAGED INTO SECRETORY GRANULES AND RELEASED IN EQUIMOLAR AMOUNTS!

Sulfonylureas increase insulin secretion and hence C peptide in type 2 diabetes

Question 11

Two Bacillus anthracis virulence factors

Answer 11

1. antiphagocytic polyD glutamic acid capsule
2. anthrax exotoxin that is trimeric made up of protective antigen with translocates Edema factor (like Bordellas calmodulin dependent AC toxin) and lethal factor…PROTECTIVE FACTOR NEEDED for EF and LF to work

Question 12

Centro versus Pan acinar Emphysema Pathogenesis

Answer 12

Centroacinar (heavy smoker with exertional dyspnea and airspace enlargement on CT):- oxidative injury to respiratory bronchioles, resident macrophages activated, recruitment of neutrophils to airspacem these realease MMP, proteinase 3, elastate, cathepsin G. Activated M’s release proteases…Neutrophils activated generated ROS which prevents alpha antitrypsin antiprotease. ..BUT ELASTASE in excess from neutrophils is KEY

Panacinar:- Usually due to alpha 1 antitrypsin activity- the major neutrophil elastase inhibitor

Question 13

Histological changes in respiratory tract

Answer 13

Bronchi:- Pseudostratified columnar ciliated, goblet cells, submucosal mucoserous glands and cartilage.
Bronchioles, terminal bronchioles and respiratory brionchioles lack goblet cells, glands and cartilage
Terminal Bronchioles level:- Ciliated simple cuboidal
Epithelial Cilia persist to the end or respiratory bronchioles

Submucosal mucous and serous glands travel in cartilaginous plates in the tracheobronchial tree and end at the smallest bronchi

-BRONCHIOLES LACK GOBLET CELLS, GLANDS and CARTILAGE GENERALLY

Question 14

Histological changes in respiratory tract

Answer 14

Bronchi:- Pseudostratified columnar ciliated, goblet cells, submucosal mucoserous glands and cartilage.
Bronchioles, terminal bronchioles and respiratory brionchioles lack goblet cells, glands and cartilage
Terminal Bronchioles level:- Ciliated simple cuboidal
Epithelial Cilia persist to the end or respiratory bronchioles

Question 15

Atheromas

Answer 15

Plaque with a fibrous cap that undergoes remodelling
Keeps it stable
Activated macrophages can make MMPs to degrade collagen
Intimal inflammation can destabilize plaques leading to rupture, acute coronary syndrome and MI

Question 16

Female Gamatogenesis

Answer 16

• Starts at 4 weeks gestation (primordial germ cells migrate from yolk sac to gonadal region)
• Differentiate into oogonia (46, 2N) then start meiosis I
• Meiosis 1, primary oocytes (46, 4N), arrested in meiosis 1 until puberty
• By 5 months all oocytes formed. Degenerate throughout life to menopause
• With FSH at puberty, oocytes stimulated to complete meiosis 1
• Secondary oocytes formed with polar bodies (23, 2N)
• Secondary stats meiosis II, polar body degenerates. Halts in metaphase II
• By Day 14, secondary released due to paradoxical LH surge from high estrogen.
• Secondary frozen in metaphase of meiosis II until fertilization
• With fertilization divides into mature oocyte and second polar body

Question 17

Diabetes Complications two pathways

Answer 17

1. Advanced glycosylation end products:- glucose attaches to amino acid residues, accumulate and becomes irreversible. Attaches to collagen, blood vessel, tissues leading to microangiopathy and nephropathy. This facilitates inflammation and LDL deposits hence atherosclerosis
2. Polyol pathway in tissues that dont depend on insulin for glucose transport (kidney, peripheral nerve, lens, blood vessels). GLucose- sorbitol (aldose reductase)- fructose..High osmotic pressure, hence injury, in lens opacification and cataracts, in schwann cells, peripheral neuropathy

Question 18

Holiday Heart Syndrome

Answer 18

Binge drinking can lead to palpitations (subjective awareness of heart beating), AFib:- irregularly irregular tachy (QRS, absent p waves), pericarditis, increased sympathetic tone

Question 19

Cytokines, and chemotactic factors

-Neutrophils

Answer 19

NEUTROPHILS

• IL8 is pro neutrophils and C5a is pro every wbc type while C3a is ONLY EOSINOPHILS AND BASOPHILS
• LTB4 and 5HETE are also pro neutrophil

OTHERS

• IL10 is anti inflammatory
• IL3 secreted by active t cells leads to bone marrow cell differentiation

Question 20

LEPTIN

Answer 20

Enhances satiety. HOW
- Increases POMC, this gets cleaved to aMSH which decreases eating
-Decreases NPY4 which makes you eat
These substances are made in the arcuate nucleus of the hypothalamus

Question 21

Schizosss

-Distinguish schizophreniform from schizoaffective

Answer 21

Schizophrenia Symptoms are
Psychosis (Hallucinations, Deluisions, Disorganized Speech) and NEGATIVE SYMPTOMS. Need 2

If Schizophreniform, need 2 or more of schizophrenic symptoms plus 1-6 months of episodes…rarely mania
If Schizoaffective need PROMINENT mood symptoms in addition to schizophrenic symptoms. Also need 2 wks of psychosis in absence of mood

Question 22

Narcolepsy Drug

Answer 22

First line is Modafinil, a stimulant which is thought to act via dopamine
Second line is Amphetamines but due to increased sympathomimetic effects are not used as often

Question 23

Zolpidem

Answer 23

A non-benzo anti insomnia drug

Question 24

Tibial Nerve

Answer 24

Plantar flexion

Plantar foot/sole of foot sensation

Question 25

Kidney Metabolic Compensation Timeline - How does overuse of diuretics present - What about heroin

Answer 25

Timeline is 3-5 days Diuretics abuse can lead to contraction alkalosis, hence aldosterone secretion, hence proton loss hence alkalosis Heroin overuse leads to respiratory depression which acutely causes respiratory acidosis, later compensated with bicarb (initially bicarb is low)

Question 26

Mode of action of benzos vs barbiturates

Answer 26

Benzo's increase the frequency of GABA channel opening while Barbiturates increase the duration of opening

Question 27

Anatomy of the abdomen, - where does the aorta bifurcate - What does the ileum resemble on CT - which renal vein drains the gonadal vein - Describe the pathway of the renal vein - What can be mistaken for IVC on CT - At what level can we see both kidneys

Answer 27

- Aorta bifurcates at L4 - Ileum looks like an 8 - On the left the left gonadal vein drains into the left renal vein - Renal vein goes anterior to the aorta but posterior to the SMA then drain in the IVC - Dont mistake duodenum for IVC,. IVC is next to the aorta right in front of vertebral bodies - L2 is the level at which both kidneys can be imaged

Question 28

Increased ACTH has whhat effect on the kidney

Answer 28

HYPERPLASIA not hypertrophy of both the Fasiculate (Cortisol) and Reticulata (sex hormones_

Question 29

Trisomy 18

Answer 29

AKA Edwards - Microcephaly - Low set ears - Small mandible - Fist clenched

Question 30

Which lifestyle modification is tantamount

Answer 30

SMOKING CESSATION

Question 31

COngenital bicuspid aortic valves

Answer 31

sixth decade calcific aortic stenosis!!! These tend to be asympathomatic, no murmors or outflow tract issues, in contrast to congenital aortic stenosis!!!!

Question 32

Hepatitis B antigens

Answer 32

- s Ag comes up first, before symptoms and peaks when most ill, undetected in 3-6 months unless chronic phase - Shortly after HBsAg is HBeAg and HBV DNA:- active viral replication - (shortly before onset of symptoms, there is anti-HBcAg and increased serum transaminases) - anti-HBcAg IgM is replaced with IgG OVER next months - anti-HBeAg appears after HBeAg vanishes hence transtion from high viral replication and infectivity to lower. - Anti HBsAg IgG rises post resolution of acute phase UNLESS chronic phase

Question 33

Pituitary Apoplexy

Answer 33

Acute bleed into pituitary adenoma - Sudden headache and cranial nerve paralysis. Signs of meningeal irritation - CV collapse if adrenocortical crisis Same as berry aneurysm rupture EXCEPT visual field pituitary apoplexy

Question 34

Sheehans

Answer 34

Postpartum women - Ischemic necrosis of the pituitary - Indolent - Failure to lactate

Question 35

Aortic Stenosis sounds, causes

Answer 35

Cres-Decrescendo Systolic ejection Right sternal border -Exertion/Syncopie -Causes Congenital abnormal valve with calcification (e.g. bicuspid aortic valve, calcified normal valve (more common US), rheumatic heart disease (more common worldwide)

Question 36

Lynch Syndrome

Answer 36

Hereditary non polyposis colon cancer. Autosomal dominant. Defective DNA mismatch repair - mutS (detects mismatch) and mutL (loads exonuclease 1) homologs. coded for by MSH2 and MLH1 involved in 90% mutations - Normal DNA polymerase proofreading still leads to errors every 10^6 base

Question 37

Samsters triad

Answer 37

-Asthma -Aspirin hypersensitivity (nasal symptoms, , facial flushing bronchospasm ) -Nasal polyposis Occurs in 10% of asthmatics treated with aspirin due to Leukotriene overproduction!!! (aspirin blocks COX!!!)

Question 38

High dose aspirin causes

Answer 38

Salicylism -Vertigo -Tinnitus -Hearing loss Can cause Hyperpnea via stimulation of respiratory drive hence -respiratory alkalosis -salicylate accumulation leading to metabolic acidosis

Question 39

Effect of steroids on liver, peripherally

Answer 39

Potent stimulators of liver glucooneogenesis., glycogenesis - Stimulate PEP carboxykinase - Glucose 6 phosphatase - Glycogen synthase (increased glycogen reserve in terms of stress) Peripherally -Antagonize insulin -Favors catabolism (proteolysis and lipolysis) Hence muscle weakness, skin thinnning, impaired wound healing, osteoporosis and immunesuppresion, hyperglycemia

Question 40

Cox 1 and 2 expression

Answer 40

COX 1 is constituitively expressed and 2 is undetectable except in activated inflammatory cells , hence is inducible and is 72kD

Question 41

Mycoplasma and Ureaplasma

Answer 41

LACK PEPTIDOGLYCAN CELL WALL -RESISTANT TO AGENTS THAT ATTACK THE WALL NO penicillins, cephs, vanc, carbapenems USE ANTI RIBOSOMALS LIKE tetracycline and erythromycin

Question 42

Dilated CDM causes

Answer 42

``` Viral myocarditis (Coxsackie B) Peripartum cardiomyopathy Alcohol Chronic SVTs Cardiotox drugs e.g. doxorubicin Thiamine Deficiency (Wet beriberi) ``` IT IS A DIAGNOSIS OF EXCLUSION

Question 43

On what chromosomes are these tumor suppressor genes (diseases in bracket) - VHL - RB - NF-1 - WT-1 - BRCA-1

Answer 43

``` VHL- 3 (RCC in 40% cases, cerebellar hemangioblastoma, Pheos!) RB-13 (RB and osteosarcoma) NF-1 -17 (NF-1) WT-11 (Wilms tumor) BRCA1- ovarian and breast ```

Question 44

Adenomatous polyps - Describe them histologically - Genetic changes - Malignant?

Answer 44

Dysplastic mucosa Premalignant >50 yrs old Mutations in APC tumor suppresor Stepwise progression to adenocarcinoma with mutations in KRAS, p53 and DCC INCREASED COX2 activity in some forms of colon AC/inherited polyposes. HENCE ASPIRIN CAN LEAD TO LOWER INCIDENCE

Question 45

Ectoderm has three components

Answer 45

- Surface Ectoderm - Neural Tube - Neural Crest

Question 46

What are derivatives of surface ectoderm

Answer 46

- Rathkes pouch/anterior pituitary - Lens and cornea - Inner ear sensory organs - Olfactory epithelium - Nasal and oral epithelial linings - Epidermis - Salivary Gland - Sweat and mammary glands

Question 47

Neural Tube

Answer 47

- Brain and spinal cord - Posterior Pituitary - Pineal Gland - Retina

Question 48

Neural Crest

Answer 48

- A/P septum and endocardial cushions - Autonomic/Sensory/Celiac Ganglia - Schwann cells - Pia and arachnoid matter - Branchial arches (bones AND cartilage) - Skull bones - Melanocytes - Adrenal medulla

Question 49

Mesoderm

Answer 49

- all 3 kinds of muscles - Connective tissue - Bone and cartilage - Serosa linings of peritoneum - cardiovascular system - Blood - Lymphatic system - Spleen - Internal Genitalia - Kidney and ureter - Adrenal cortex

Question 50

Endoderm

Answer 50

``` GI tract Liver Pancreas Lung Thymus Parathyroid Follicular cells of thyroid Middle ear Bladder Urethra ```

Question 51

T cell maturation - Where are the cells made - When and Where do they mature (what processes exactly happen here) - Where do positive and negative selection occur

Answer 51

- Made in bone marrow and mature in thymus in FIRST trimester of gestation. - Thymus (TCR arrangement, positive and negative selection, extracellular markers and co-stim expression) - Come in negative - B chain of TCR expressed - Begin to be doubly positive - A chain expressed - Positive selection in thymus cortex and negative in medulla - Loss of either CD4 or CD8