Block 36

Question 1

Saccular stage of lung development,

Premature birth

Answer 1

• in the terminal saccular stage of lung development, the type II pneumocytes produces pulmonary surfactant, a lipoprotein complex rich in phospholipids, most notably DPPC.
• this surfactant decreases alveolar surface tension by creating lipid rich monolater that seperate alveolar gas from the underlying aqueous fluid.
• efflux of lung into amniotic fluid enables testing of markers lung maturity, untill 33 week of gestation, the L and S values are about equal, after 33 weeks the L levels rises dramaticly compared to S.
• L/S ratio of 1.9 is indicative of mature fetal lungs.

Question 2

Alzehaimer disease biochemical abnormality

Answer 2

The most important biochemical abnormality seen in alzehaimer disease is decrease in Ach levels. This occurs due to deficiency of choline actyltransferase.

• the decline in actyltransferase is most notable in the basal nucleus of meynert which precipitates in momory and cognition.
• the nucleus is located at the base of forebrain and widely projects to the neocortex.
• another involved structure is the hippocampus, the major function of it is formation of new memories.

Question 3

Medication that selectively binds to IL-1 inducible enzyme that is highly expressed by inflammatory cells and undetectible in surrounding normal tissue

Answer 3

COX-2 inhibitor - celecocxib in gout.
-COX-2 is an inducible enzyme that is undetected in most tissues normally. during inflammation, infiltrating cells secrete cytokines (IL-1, TNF-å) that causes COX-2 upregulation in the inflamed tissue.

Question 4

Polycythemia vera mutation

Answer 4

PV is caused by abnormal transduction of EPO growth signals.
The erythropoietin receptor has no intrinsic kinase activity and must interact with JAK2, a cytoplasmic (non-receptor) tyrosine kinase, to initiate downstream signaling. All pts with PV have mutation in JAK2 that causes constitutive activation of its kinase domain, resulting in clonal proliferation of myeloid cells. JAK2 mutation have also been implicated in essential thrombocythemia, primary myelofibrosis and other myelproliferative disorders.

Question 5

Recombination

Answer 5

Refers to the exchange of genes between 2 chromosomes via crossing over within homologous regions. The resulting progeny can have recombined genomes with traits fro both parent viruses. This usually occur in nonsegmented viruses such as herpes virus (unlike reasorment which occurs in segmented virus such as infleuenza)

Question 6

Phenotypic mixing

Answer 6

Occurs when a host cell is coinfected with 2 viral strains and progeny virions contains parental genome from one strain and nucleocapsid (or envelope) proteins from the other strain.
-this may result in a progeny acquiring additional traits (eg, enhanced ability to infect new host cells due to different nucleocapsid proteins).

Question 7

Brunner glands

Answer 7

Secrete copious amounts of alkaline mucus into the dudenoum, they are found within the first part of duodenum. These glands are most numerous at pylorus but may be found intermittently up to the ampulla of vater.
-the ducts of these glands pass through the muscularis mucosa and terminates in the mucosal crypts.

Question 8

Which side effect would persist even after adding carbidopa to levodopa treatment

Answer 8

Anxiety and agitation.

• anxiety is increased because more dopamine is available to the brain. Adding carbiodopa inhibits the peripheral conversion levodopa, making more of it available to the brain.
• high dose combination levodopa/carbidopa, can cause various behavioral changes such as anexiety, agitation, insmonia, confusion, delusions and hallucinations. Reducing the dose is helpful in alleviating these adverse effects. If reduced dosage is not possible, atypical antipsychotics, such as clozapine, may be helpful.

Question 9

Drug that act on enahancing postsynaptic chloride influx in status epliepticus.

Answer 9

benzodiazepines enhances the effect of the inhibitory neurotransmitter GABA-A, a ligand gated ion channel. Allosteric attachment of benzodiazepines to the GABA-A receptor causes increased influx of negatively charged chloride ions in response to GABA binding.
-this leads to hyperpolarization of postsynaptic neuron and suppression of action poteintial firing.

Question 10

Pathogenesis of congestive heart failure

Answer 10

Heart failure occurs when a structual or functional cardiac disorder impairs ventricular filling or ejection of blood causing reduced CO and excessive ventricular filling pressures.

• the reduced CO is detected as an initial drop in BP which triggers compensatory neurohumoral stimulation directed at maintaining BP and tissue perfusion.
• this compensatory response is mediated cheifly through increased in “symphathetic nervous system activity, stimulation of RAAS and release of ADH.
• however these adaptation often lead to severe consequences such as -increased afterload from excessive vasoconstriction can further impede cardiac output and lead to excess fluid retention due to poor renal perfusion.
• high-renin angiotensis activity also increases fluid retention, which contributes to peripheral edema and pulmonary congestion. Heart failoure symptoms of circulatory overload is often called congestive HF.
• deleterious cardiac remodelling occurs secondary to hemondynamic stress and neurohumoral stimulation thereby prepetuating a downward spiral of progressive cardiac deterioration.

Question 11

Left atrial appendage

Answer 11

Is small saclike structure in left atrium that is particularly susceptible for thrombus formation.
-approximately 90% of left atrial thrombi are found within LAA in patients with nonvalvular atrial fibrilation

Question 12

Why verapamil doesnt affect skeletal muscle

Answer 12

Due to the fact that it has little dependence on extracellular calcium influx.

Question 13

Hydrocephalus, intracranial calcification and chorioritinitis in infant

Answer 13

• its a classic triad of toxoplasmosis.
• hydrocephalus occurs due to CNS inflammation and is evidenced by macrocephaly and enlargement of ventricles.
• chorioretinitis refers to inflammation of the choroids and the retina that can leave cotton like white/yellow scars.
• its transmitted to fetus in utero

Question 14

Intrapartum infection (during delivery) in infants

Answer 14

• infection with HSV
• opthalamia neonatum refers to neonatal conjuctivitis caused by number of agents such as chlamydia, nisseria and viruses.

Question 15

Erythropoiesis stimulating agents are associated with

Answer 15

• increased risk for thromboembolic events
• increased blood viscosity as a result of the elevation in red cell mass, many patients develops hypertension, possibly due to activation of EPO receptors on vascular endothelial and smooth muscle cells.

Question 16

Foreign bodies on skin

Answer 16

Foreign bodies can elicit a granulomatous response seen clinically as tender erythmatous brown or purple papule, plaque of nodule.
-microscopically granulomas are characterized by aggregates of activated macrophages that assume an eptheloid appearance.

Question 17

Dystonia is

Answer 17

Neurological movement disorder charactrized by sustained,involuntary muscle contraction which force certain parts of the body into abnormal, sometimes painful movement or posture.

• these movement may affect a single muscle, group of muscles or the entire body.
• focal dystonias involve one muscle or one muscle group. Cervical dystonia, also called spasmodic torticollis is the most common of the focal dystonia.
• blepharospasm is the second most common focal dystonia. Its involuntary, forcible closure of eyelid.
• writer camp affects the muscles of the hand.

Question 18

Leuprolide

Answer 18

GnRH analog. It has agonist proprties when administred in pulsatile fashion and can cause a transient rise in LH and testosterone production on initial administration.
However contineous GnRH stimulation, whether from a GnRH infusion or long term supresses LH release —> decreased testosteron and DHT. However the in the beginning the drug might actually elevate the testosterone then decrease it

Question 19

What is the cause of symptoms (lathergy,vomiting, diarrhea, enlarged fontanele etc..) in CF patients

Answer 19

Hyponatremia due to excessive salt wasting from the sweat.
-risk factors for hyponatremia in patients with CF include exclusive breast or formula feeding prior to introduction of sodium rich, solid foods, exposure to high tempreture and exercise. Therefore salt supplementation is recommended for CF patients.

Question 20

TNF-a effect on insulin receptor

Answer 20

TNF-a is proinflammatory cytokine that induces insulin resistnace through the activation of serine kinases which then phosphorylates serine residues on beta subunit of insulin receptor (IR) and IRS-1. This inhibits tyrosine phosphorylation of IRS-1 by IR and subsequently result in downstream signaling, resulting in resistance to normal action of insulin.

Question 21

How does epinephrine and glucagon counteract insulin

Answer 21

Via stimulation of serine phosphorylation that will result in inhibition of receptor autophysphorylation and tyrosine phosphorylation of insulin receptor substrate

Question 22

Gluts

Answer 22

Of the major 5 GLUT, only GLUT-4 is responsive to insulin.
GLUT 4 is expressed predominantely in skeletal muscles and adipocytes. In the absence of insulin ,GLUT-4 is sequestered in the cytoplasm and the cells are imperable to glucose. However, as insulin concentration rise, the receptors translocate to the plasma membrane, facilitating glucose transport into the cell.
GLUT1,2,3,5 are always present in plasma and are insulin independent.

Question 23

GLUT-2

Answer 23

Present in hepatocytes, ß-pancreastic cells and the basolateral membrane of renal tubules and small intestinal mucosa.
-it plays a role in absorption of dietary glucose.

Question 24

Wilson disease complications

Answer 24

• hepatic cirhosis
• kayser flischer rings
• basal ganglia atrophy

Question 25

How to prevent intravascular catheter related infections

Answer 25

1. Hand hygiene with alcohol sanitizer or soap prior to donning sterile gloves 2. Maximal barrier precautions (mask, gloves, long sleeved surgical gown ..) 3. Chlorhexidine antiseptic preperation of insertion site 4. Use of subclavian or internal jugular as femoral vein have high risk for infection 5. Removal of catheter is no longer needed.

Question 26

The most important opsonin in the body

Answer 26

IgG and c3b. After opsonin are bound to cell surface they act as a handle for receptors on phagocytes to grasp, allowing the phagocytes to more easily engulf foreign cell. - the importance of C3 is demonstrated by the fact that all 3 complement pathways (lectin,classical and alternative) converge on it resulting in cleavage into C3a and C3b. In addiotion to act as opsonin, C3b can also tigger MAC. - Igm can be a potent stimulator of c3b opsonization however, there is no receptor on MACrophage for the FC portion of IgM and it doesnt directly enhance phagocytosis.

Question 27

Hypoketotic hypoglycemia is most likely to enzyme deficiency in

Answer 27

Acyl-coa synthase. | (Medium chain acyl-coa dehydrogenase)

Question 28

What is the most important factor in diagnosing tetanus

Answer 28

History, and physical examination. Lab test usually not effecient in diagnosis tetanus (there is no serum toxin assay available for tetanus, and the blood culture arent much of a use because tetanus bacteria is present in the wound not in the blood)

Question 29

Frontotemporal dementia (picks disease)

Answer 29

Charactrized by degeneration of the frontal lobes that eventually progress to include the temporal lobes. - characteristic symptoms include early personality and behavioral changes such as disinhbition, apathy, social inappropriateness and compulsive behavior and altred speech patterns. - it should be differentiated from alzheimer disease.

Question 30

Overflow incontinence findings

Answer 30

Increased postvoid residual volume | Its most commonly due to impaired detrusor contractility or bladder outlet obstruction.

Question 31

Metalloprotinases are

Answer 31

Zinc containing enzymes that degrade components of the ECM and basement membrane which are composed primarily of laminin and collagens IV and VII. These enzymes participates in many physiologic process such as tissue remodelling and embryogenesis. -they also facilitate basment membrane penetration which distinguishes an invasive tumor from carcinoma in situ.

Question 32

Lymphatic drainage of scrotum vs testis

Answer 32

- drainage of scrotum occurs via the superficial inguinal lymph nodes. These lymphnodes drain nearly all cutaneous lymph from the umbilicus to the feet. - lymph nodes from the testes drains directly into para-aortic lymph nodes. - lymph nodes from glans penis and cutaneous portion of posterior calf drains into the deep inguinal lymph node.

Question 33

Biopsy of cerbellum shows sheet of primitive cells and many mitotic figures along with ataxia symptoms

Answer 33

Medulloblastoma. The most common location is cerbellar vermis . Medulloblastoma are part of a group called primitive neuroectodermal tumors which are composed of sheets of small cells with deeply basophilic nuclei and scant cytoplasm.

Question 34

Adenoma to carcinoma sequence

Answer 34

Most colon adenocarcinoma develop from preexisting adenomatous polyps (adenomas). Colon adenomas usually occur in patients in their 50s and 60s and are considered premalignant. Progression of adenoma to carcinoma : 1. Progression from normal mucosa to small adenomatous poly (adenoma) , mutation in APC. 2. Increase in the size of adenoma. This is due to mutation in KRAS protoncogene by leading to uncontroleld cell proliferation. KRAS mutation inactivates (GTPase) 3. Malignant transformation from adenoma to carcinoma involve mutation in TP53. Aspirin impedes this process due to inhibition of COX

Question 35

Muscle cramps with thaizide diuretics is usually due to

Answer 35

Hypokalemia, it can lead to muscle weakness, cramps and possible rhabdomyolysis. -hyponatremia rarely leads to muscle weakness and usually associated with chronic hyponatremia.

Question 36

Biceps brachi innervation

Answer 36

Musclucutaneous nerve, which arises from the lateral cord (c5,c6,c7) .if injured biceps reflex would be absent. It also innervates coracobrachialis and brachialis.