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Terms in this set (112)

Patient has stable angina (angina pectoris) d/t underlying CHD.

Aspirin irreversibly inhibits COX. Inhibiting COX1 in palettes prevent synthesis of thromboxane A2, a potent stimulator of platelet aggregation and vasoconstriction = reduce the risk of occlusive thrombus formation and subsequent MI.

Some patients are unable to tolerate aspirin d/t exacerbation of preexisting respiratory symptoms (eg, rhinos and asthma) or delveopment of allergy reactions (eg, urticaria, angioedema, anaphylaxis). A good alternative for these patients is Clopidogrel:

MOA: blocks the P2Y12 component of ADP receptors on the platelet surface and prevent platelet aggregation.
-it is as effective as aspirin for prevention of cardiovascular events and should be used in patents with aspirin allergy.

a/g. Apixaban is direct factor Xa inhibitor that prevents platelet activation and fibrin clot formation. Warfarin inhibits enzyme required for synthesis of active vitamin K, resulting in decreased synthesis of vitamin K-dependent clotting factors (II, VII, IX and X). Both of these meds are typically used for prevention and/or treatment of thromboembolic events, not CAD.

b. cilostazol is a phosphodiesterase inhibitor that occasionally used in patients with symptomatic peripheral vascular disease (i.e., claudication)

d. low molecular weight heparins (LMWHs; enoxaparin, dalteparin) are indirect thrombin inhibitors that bind with antithrombin and convert it form a slow to a rapid activator of thrombin and factor Xa. They are used in patients with acute coronary syndrome (unstable angina or MI) but have no role in the management with stable angian.

e. eptifibatide is a platelet glycoprotein IIb/IIIa inhibitor that inhibits the final common pathway of platelet aggregation. It is occasionally used in some patients with acute coronary syndrome, but not for stable CHD.

f. naproxen is an NSAID used for pain and management in patients with osteoarthritis. Use of both nonselective and selective COX2 NSAIDSs increases the risk adverse CVS event.s
Diverge = no 3rd or 4th pharyngeal pouch derivatives = thyme aplasia = immunodeficiency from extremely low number of mature T lymph.

-T-lymph are made in bone marrow but mature in thymus. Therefore patients are predisposed to recurrent infections by viral, fungal, protozoan and intracellular bacterial pathogens.

-paracortex is the region of the lymph node where T lymph and dendritic cells chill. It lies internal to the cortex, between the follicles and medulla Dendritic would present antigens they collect form blood and lymph to the aggregated T-lymph in this region. The paracrotex becomes enlarged by the proliferation of T lymph during adaptive cellular immune response (eg, viral infections). In DiGeorge syndrome, this region is poorly developed d/t def of mature t lymph.

a. Located in the outer cortex, the follicles are sites of B lymphocyte localization and proliferation.
-Primary follicles: dense and dormant
-Secondary follicles: pale germinal center containing proliferating B cell and folliculrlar dendritic cells. In agammaglobulinemia, germinal centers and primary lymphoid follicles do not form d/t an absence of B cells

b/c. In the medulla you have cords and sinuses. The former contain B cells, plasma cells and macrophages, while the latter only have reticular cells and macrophages.

e. the sub capsular sinus are the regions lying between the capsule and cortex of the lymph node. They are in direct communication with afferent lymphatic vessels and the cortical sinuses that line the trabecular. the cortical sinuses are continuous with medullary sinuses and the single efferent lymphatic channel existing the hilum.
Cyanide toxicity is dependent upon its ability to bind to Fe+3 (ferric) with high affinity, inhibiting cytochomre c oxidase in the mitochondria. This inhibits oxidative phosphorylation causing lactic acidosis and death as a result of cells switching to anaerobic metabolism

Clinical presentation
-nausea/vomiting, confusion and weakness.

Labs: lactic acidosis in conjunction with narrowing of the venous arterial PO2 gradient, resulting for the inability of tissue to extract arterial oxygen.

Treatment: inhaled amyl nitrite oxides ferrous iron present in hemoglobin to ferric iron generating methemoglobin. Methemoglobin is incapable of carrying oxygen but has high affinity for cyanide; it binds and sequesters cyanide in the blood, freeing cytochrome oxidase and limiting its toxic effects. Hydroxycobalamin, a vitamin B12 precursor, and sodium thiosulfate are also antidotes for cyanide poisoning. there interaction with cyanide generate relatively nontoxic metabolites that are easily excreted in the uric.

a/b: 2,3-BPG causes a rich shift in the oxygen-hemoglobin dissociation curve, decreasing hemoglobin affinity to O2 but increasing its affinity to CO@

c. Hemoglobin has much higher affinity for CO than it does for oxygen. This is the basis for carbon monoxide poisoning, which is treated with high for oxygen.

e. the affinity of hemoglobin for iron is not affected by nitrite administration, although nitrites do oxide the heme iron to its ferric state.

f. Lead poisoning causes defect heme synthesis. If lead is acutely ingestion, chelation therapy with dimercaprol and edentate disodium calcium (CaNaEDTA) should be initiated. 0
Hansen disease affects skin and nerves

Etiology: Mycobacterium lapra. Transmission via respirator or prolonged skin to skin contact. Associated with the armadillo in the southwestern US.

It likes low temperature which makes sense why the clinical manifestations occur in the skin, balls and superficial nerves.

Path: depends on how strong Cell Mediated Immune responses are, which gives us two types of leprosy
1) tuberculoid (TL): least severe. patient has intact CMI that will launch a Th1-mediated response. Mild skin plaques will develop that are hypo pigmented. Hair follicle loss and focally decreased sensation.
2. lepromatous (LL): most severe. patient has weak CMI that will launch a Th2-mediated response. Macrophage signaling to kill M leprae is limited which will lead to: skin thickening, plaque like hypo pigmentation (often with hair loss), leonine facies, paresis, regional anesthesia, testicular destruction and blindness

a. B. burgdorferi cause Lyme diseases. Erythema chronicum migrant with fever and malaise. Systemic disease can cause arthritis, facial paresis or cardiac involvement (eg, condition abnormalities). Prolonged untreated diseases will have CNS involvement.

b. Campylobacter fetus, a gram - rod, causes mild enteritis in immunocompetent and mild systemic bacteremic illness in immunocompromised

c. C. dish is a gram + rod. Clinical manifestations are often toxin mediated that can lead to lower respiratory tract infection. Complication can cause polyneuritis and myocarditis.

e. T. palladium causes syphilis.
-Primary: painlesss chancre
-Secondary: diffuse erythamtous macule over the entire body including palms and soles and condyloma late formation
-Tertiary: syphilis results in skin and bone gammas and ascending aortitits
Hepatic processing of bilirubin
1. carrier mediated uptake of bilirubin at the sinusoidal membrane
2. conjugation via UGT (urdine diphosphate-clucuronyltransferase) in ER
3. Biliary excretion of water-soluble, nontoxic bilirubin glucuronides.

Disruptions of these processes can lead to Crigler-Najjar syndrome.
-Type 1: AR. Lack of UGT enzyme. Unconjugated hyperbilirubinemia will develop.

Conjugated bilirubin is water soluble and loosely bound to albumin = easy excretion
Unconjugated bilirubin are less soluble and binds tightly to albumin = not excreted, that will graduallydeposited into various tissues, including the brain. Kernicterus (bilirubin encephalopathy), can be fatal.

b. Dubin-Johnson is AR. Absence of biliary transport protein, MRP2 (multi drug resistance protein 2), used in the hepatocellular excretion of bilirubin glucuronides into bile canaliculi. Liver is darkly pigmented, however disease is asymptomatic

c. rotor syndrome is rare AR d/t asymptomatic conjugated hyperbilirubinemia that results from numerous defects in the hepatic uptake and excretion of bilirubin pigments. Although patients are often jaundiced, they enjoy normal life expectancies.

d. High amount of anaerobes and S. aureus can deconjugate bile acids (via removal of glycine and taurine), rendering them less soluble and therefore less able to form micelles. This beconjugation impedes the active reabsorption of bile acids into portal circulation at the terminal ileum, resulting in lipid malabsorption. However, there are no neurologic abnormalities associated with bilirubin beconjugation in the gut

e. in the colon, bacterial enzymes reduce bilirubin into urobilinogens, where a small fraction returns to the liver where they will later either re-enter GIT or excreted via urine. Urobilinogens that remain in the colon are excreted in the feces as stercobilin, contributing to its dark color. Fortunately, there are no neurologic abnormalities associated with impaired gut reabsorption of bilirubin.
PAH is filtered from the blood in the glomerulus and screwed by the PCT. Because it is both filtered and secreted, it can be use to estimate RPF.

Filtration cannot be saturated, however excretion mediated career enzyme mediated process that can be saturated. Therefore, as blood concentrate not PAH increases, the secretion of PAH by PCT increases, but only up to a maximum value of approximately 80 mg/min. Pass this point, secretion plateaus and any increases in the uric PAH concentration are d/t increased filtration.

a. excretion of a substance is defined as = filtration + secretion - reabsorption. Once carrier mediated secretion and reabsorption mechanisms are saturated, these processes are at their maximal rater. However, filtration is not enzyme or protein mediated, so it doesn't show maximal value. Because filtration cannot be saturated neither can excretion.

b. the maximal reabsorption rate doesn't apply to PAH, which is a secreted substance. Glucose is example of substance that is aggressively reabsorbed in the proximal tubule. Under normal conditions, no glucose is lost in the urine, despite the fact that glucose filtered into Bowman's space. In uncontrolled diabetes, however, glucose is seen in the urine because the reabsorption carrier proteins become saturated at very high glucose concentration

d. filtration fraction is decreased by decrease in GFR or increase in RPH

e. RPF is decreased by factors that constrict blood vessels in the kidney such as epinephrine, NE and angiotensin II
CN V: exits brain stem at the ventrolateral pons. Injury would lead to loss of:
-Ipsilateral facial sensation
-conreal reflex (afferent limb)
-paralysis of muscle of mastications

CN VI: exits brain stem from the pontomedullary junction medial to the facial nerve. Lesion leads to:
-inability to abduct ipsilateral eye
-horizontal diplopia (lack of innervation to the lateral recutus)

CN VII: exits the brain stem from the ventrolateral pontomedullary junction, just lateral to the abducens. Damage would cause:
-ipsilateral facial muscle paralysis (upper and lower)
-Loss of corneal reflex (efferent limb)
-Loss of taste in the anterior two-thirds of the tongue
-hyperacusis (no innervation to the stapedius)

CNVIII: exits the brainstem from the pontomedullary junction, lateral to CNVII and enters the cerebellapontine angle. Lesion would cause:
-hearing loss and tinnitus from impairment of the cochlear portion of the nerve.
-vertgio, dysequilibirum and nystagmus

CN IX: exits the brain stem from the postolivary sulcus in the medulla just rostral to the vagus nerve. Injury would cause:
-loss of base/sensation in the posterior 1/2 of the tongue.
-no gag reflex (afferent limb)

CN X: exits brain stem from the postolivary sulcus just caudal to CN IX. Damage would cause:
-dysphonia (lack of innervation to the laryngeal muscles)
-impaired swallowing with inability to elevate soft palate (lack of innervation to the pharyngeal muscles)
-Lack of gag reflex (efferent limb)

CN XI: exits the from lateral medulla and upper segment of the cervical spinal cord. Injury would lead to
-weakness on head rotation away from the side of the lesion (SCM)
-ipsilateral shoulder droop (TRAP)

CN XII: exits the medulla from the postolivary sulcus medial to CN IX and X, but caudal to CN IX and rostral to CN X.
Methionine can be metabolized into S-adenosyl-methionine (SAM), which acts as a methyl donor for many methyltransferase reactions.

After transfer of methyl group, SAM is converted into S-adenosyl-homocysteine (SAH), which is broken down to form adenosine and homocysteine.

Homocysteine can be converted to cystathionine (via cystathionine synthase and B6). Cystathionine can then be converted into cysteine (via cystathionase and B6).

Homocysteine can be converted back into methionine (via methionine synthase and B12).

Homocystinuria is a condition that can lead to hyper coagulability and thromboembolic occlusion b/c homocysteine is prothrombotic. People with deficiency of methionine synthase can develop premature acute coronary syndrome, ectopic lentil (ocular lens displacement) and intellectual disability.
-this is the most common cause of homocystinuria, thus cysteine is an essential amino acid to them.

a. asparagine synthase converts aspartate to asparagine, the amino acid that is essential for rapidly dividing tumor cells that cannot produce it quickly enough on their own. The chemotherapy drug asparginase decreases asparagine contraption in tumor cells and leads to lysis of these rapidly growing cells.

c,d,f. maple syrup urine (def of alpha-ketoacid DH). Def can lead to buildup of branched chain amino acids (valine, leucine and isoleucine) and their metabolites, resulting in feeding difficulties, seizures, cerebral edema and sweet odor urine

e. phenylalanine hydroxylase catalyzes the hydroxylation of essential acid phenylalanine into tyrosine. Def of phenylalanine hydroxylase is the most common cause of phenylketonuria, which results in severe intellectual disability if left untreated.
Recent history of viral esophagitis and pneumocystis pneumonia = HIV infection.

-Headache, confusion and inflammatory CSF = meningitis, most likely cause by CRYPTOCOCCUS NEOFORMANS, an opportunistic fungus that causes meningitis (or meningoencephalitis) in immunosuppressed patients.

Morphology: YEAST form ONLY! Round/oval encapsulated cells with narrow based buds.

Virulence factor: thick polysaccharide caps

Epidemiology: present in soil and pigeon droppings. Opportunistic and respiratory transmission

Infection: Lung is primary site. Most common is meningoencephalitis if disseminated

1) India ink stain
2) latex agglutination
3) Sabouraud's agar
4) Methenamine (GMS), mucicarmine stains of tissue

1) Amphotericin B and flu cytosine (acute meningitis)
2) Fluconazole for lifelong prophylaxis.

a. nonseptate that branch at wide angels = Nucor and Rhizomes species. These fungi cause infection of the paranasal sinuses in immunosuppressed patients

b. Candida albicans forms germ tubes (sprouts of true hyphae from east cells) if incubated in 37 degrees. This test helps to different C. albicans from other Candida species.

d. Spherules (round structures containing endospores) are found in the tissue form of Coccidioides immitis, which causes lung infection and disseminated mycosis, but it is not associated with meningitis.

e. Sporangium is a structure that produces and contains spores. It is present in mold fungi. Cryptococcus has only a s yeast form and thus doesn't have sporangia.
The radial nerve enters the forearm anterior to the lateral epicondyle (near the humeroradial articulation) and divides into the:
1. superficial which provides purely somatic sensory innervation to the radial half of the dorsal hand.
2. deep branch that innervates the extensor compartment muscles in the forearm. After passing through the supinator canal (eg, between the superficial and deep parts of the supinator muscle), the deep branch continues to become the posterior interosseous nerve, which innervates muscle involves extension of the finger and thumb.

Injury to the radial nerve during its passage through the supinator canal may occur d/t repetitive pronation/supination of the forearm (eg, frequent screwdriver use), direct trauma or dislocation of the radius.

Clinical presentation
-weakness on finger and thumb extension ("finger drop"_
-tricpes brachia (elbow extension) and extensor carpi radials longs (wrist extension) are typically preserved as the radial nerve branches supplying these muscles come off proximal to the supinator canal.
-Cutaneous sensory branches are similarly preserved.

A/E: Injury to the radial nerve at the axilla (eg, "crutch palsy") typically causes weakness of the forearm, ahdn and finger extensor muscles (eg, wrist drop, absent trips reflex) with sensory loss over the posterior arm, forearm and dorsolateral hand. Injury to the nerve at the mid shaft humerus (eg, radial groove) usually causes weakness of the hand/finger extensor muscles with sparing the triceps brachia and sesonry loss over the posterior forarm/dorsolateral hand.

b. carpal tunnel syndrome can result form any condition that reduces the size of the carpal tunnel and compresses the median nerve (eg, pregnancy, hypothyroidism). patients typically have pain/apresthesias affecting the first 3-1/2 digits. Thenar atrophy with weakness on thumb abduction/opposition may also be seen.

c. the coracobrachialis muscle lies deep to the biceps brachia and is perforated and innervated by the musculocutaneous nerve. Nerve injury may result in decreased strength on forearm flexion and sensory loss over the lateral forearm.

d. In the wrist, the ulcer nerve passes between the hook of hamate and the pisiform bone in the fibroosseous tunnel known as Guyon's canal. Ulnar nerve injury at this site can cause weakness on finger abduction/adducition and clawing of the 4-5th digits.

g. fracture of the surgical neck of the humerus is usually associated with axillary nerve injury. Patients may have weakness of the deltoid and trees minor muscles as well as loss of sensation in the lateral upper arm.
Mitochondrial encephalopmyopathy: neuromuscular lesions, ragged skeletal muscle fibers and lactic acidosis.

Mitochondrial disorders follow a maternal inheritance pattern because an embryo's mitochondria are inherited from the ovum only.

Mitonchdronia contain their own genome, which is vulnerable to mutations. Each cell has hundred of mitochondria, and defects in their genome may occur in any number of the mitochondria within the cel.

HETEROPLASMY: describes the condition of having different mitochondrial genomes within a single cell. The severity of mitochondrial diseases is often directly related to the proportion of abnormal to normal mitochondria within a patient's cells.

a. anticipation refers to increased severity or earlier onset of an inherited disease in successive generations.

c. penetrance is the probability that a person with a given genotype will express its associated phenotype. If all individuals within gene express its phenotype , that gene is said to have complete penetrance.

d. Mosaicism refers to the presence of 2 or more cell lines, each with unique nuclear genome, within the same individual. While patients with both somatic and gremlin masocicsm can demonstrate disease traits and also pass the disease on to their offspring, it doesn't best explain the pattern of female only transmission.

e. uniparental disomy occurs when both members of a chromosomal pair are inherited from one parent, which can cause problems d/t genomic imprinting. For instance, although most often d/t chromosomal deletions, uniparental disomy can also cause Prader-Willi and Angolan syndrome d/t loss of expression of maternal/paternal imprinted components of a critical region of chromosome 15.

In this experiment, the repeated deoxythymidine on the latex beads most likely bind to the poly A tail of a mature mRNA. Post-strancription modification of mRNA is as follows:
1. 5' capping: a 7-methyl-guanosine cap is added to the 5' end of the mRNA
2. Polyadenylation: poly-A tail is added to most eukaryotic mRNA, which are not transcribed from the DNA template, but instead, has a consensus sequence (AAUAAA) located near the 3' end of the RNA molecule directs the addition of poly-A tail. This trial protects the mRNA from degradation within the cytoplasm after it exits the nucleus.
3. Splicing. The initial pre-MRNA contains sequence from coding and noncoding regions of DNA, aka exons and introns, respectively. SPliceosomes (complex of snRNPs and other shits) remove introns containing GU at the 5' splice site and AG at the 3' splice site.

a. aminoacyl-tRNA charged with its amino acid. the clover leaf structure of tRNA consist of a 3'CCA tail (amino acid binding site); a T loop abundant in ribothymidine, pseudouridine and cytidine residues; a D loop rich in dihydrouride residues and an anticodon loop.

c. DNA promoter regions help initiate transcription by binding transcription factors and RNA pol II. Promoter regions contain consensus sequences that are typically AT-rich (eg, TATA and CAAT boxes) or GC-rich (eg, GC box)

d. rRNA is a component of the ribosome that catalyzes peptide bond formation during translation

f. telomeres are located at the ends of chromosomes and contain TTAGGG repeats, which are added by the enzyme telomerase (RNA-dependent DNA polymerase). Craig chsortening in tolemere length is though to signal programmed cell death.
contractile mechanism in skeletal muscle depends on calcium ions and proteins (myosin II, actin, tropomyosin, and troponin).

Thick filaments in skeletal muscle are comprised of myosin molecules, with the heads of the myosin molecules forming cross links with actin during muscle contraction.

The actin chains composed the thin filaments in the skeletal muscle. Tropomyosin sits in the groove between the two actin chains, covering the myosin binding sites on actin when the muscle is at rest.

Troponin molecules are small globular proteins situated alongside the tropomyosin molecules which are comprised of three subunits: T, I and C. T binds the other troponin components to tropomyosin, troponin I binds to the troponin-tropomyosin complex to actin, and troponin C contains the bind sites for calcium. During excitation contraction coupling, Ca is released from the SR. When Ca binds to troponin C, tropomyosin shifts to expose the actin binding sites for myosin, allowing contraction to occur.

a. Ach is a NT that initiates muscle contraction in response to motor neuron stimulation. Act release form the motor neuron opens post-synaptic ligand-gated ion channels, resulting in depolarization of the muscle cell Depolarization then causes release of Ca from the SR.

b. Epinephrine is a catecholamine that is not directly involved in skeletal muscle contraction. However, epinephrine stimulates beta2-adrenergic receptors to increase skeletal muscle blood flow, glycogenolysis and lipolysis.

c/d: calmodulin and MLCK are components of smooth muscle contractile mechanism.
Tetanospasmin is a protein toxin produced by C. tetani that can travel by retrograde axonal transport into the CNS.

The heavy chain of tetanospasmin binds to ganglioside receptors on neuronal membrane and the light chain inhibits release of glycine and GABA from inhibitory interneurons. Absence of these inhibitory NTs causes sustained muscle contraction or tetanus. Symptoms:
-lock jaw
-facial muscle spasm (rises sardonic)

Tetanus is prevented by the tetanus toxic (formaldehyde-inactivated tetanus toxin) vaccination. This vaccination elicits humoral immunity specific for the tetanus toxin. Tetanus immune globulin can administered during the acute treatment of tetanus and for tetanus prophylaxis after an injury if the town is grossly contaminated.

a. CD 8 lymphocytes plays an important role in viral infections. They are capable of destroying tumor cells and participate in rejection reactions

b. activated macrophages defend against intracellular organism and are principal cell type responsible for granuloma formation

c. neutrophils is responsible for phagocytosis of foreign organism. these cells play a role in non-specific innate immunity and are not effective in preventing tetanus

d. Immune defense against the majority medically important bacteria is provided by circulating antibodies that bind to microbial cells. Bound antibodies signal both macrophage phagocytosis and complement fixation, causing bacterial death. However, tetanus disease is the result of a protein toxin, not circulating C. tetani, thus, this defense mechanism is not effective against C. tetani.
Patient has acute angle closure glaucoma and has been treated with acetazolamide, a diuretic that works by inhibiting carbonic anhydrase, which is found in high concentrations in the proximal tubule and is responsible for catalyzing reactions necessary for NaHCO3 reabsorption. By inhibiting carbonic anhydrase, acetazolamide and other carbonic anhydrase inhibitor effectively block HCO3 reabsorption in the proximal tubules resulting in the enhancement HCO3 and water excretion as well as increased urinary pH and potential metabolic acidosis

Carbonic anhydrase is also present in the eyes, pancreas, GIT, CNS and RBCs. In the eye, carbonic anhydrase modulates HCO3 formation in the aqueous humor. Inhibition of carbonic anhydrase will decrease HCO3 and aqueous humor formation; thus, a number of carbonic anhydrase inhibitors are used to relieve intraocular pressures in open angle and angle closure glaucoma. Common side effects of carbonic anhydrase inhibitors include somnolence, paresthesias and urine alkalization. Rare side effects include metabolic acidosis, dehydration, hypokalemia and hyponatremia.

Loop diuretic work in the thick ascending limb and is the most potent diuretic

DCT actively transport Na and Cl and is impermeable to water. Thiazide works here.

Collecting duct system includes the collecting tubules and ducts. Here, aldosterone and ADH make final adjustment to eye trolleys and water content. Potassium-sparing diuretics and aldosterone antagonists work in the collecting duct
Lipoatrophy (lipodystrophy) is redistribution of fat from the extremities to the trunk associated with HAART (highly active antiretroviral therapy) and can be considered a product of 2 independent processes: wasting of fat from the face and extremities and deposition of fat in the trunk and viscera.
1. lipoatrophy is primarily seen in patients taking nucleoside RTIs (stavudine and zidovudine) and is also associated with protease inhibitor use
2. central fat deposition also occurs in some patients and causes increased abdominal girth and a buffalo hump (dorsocervical fat accumulation) that is similar to Cushing syndrome. Central fat deposition may be seen with any HIV treatment regimen and may be result of treatingg HIV rather than specific medication adverse effect.

Both of these syndromes have been associated with metabolic abnormalities including insulin resistance, hyperTAGs and reduced HDL.

b. statins is a HMG CoA reductase inhibitors that are associated with myalgia and an increase in hepatic transaminase levels.

c. thiazide (eg, chlorthalidone and hydrochlorothiazide) can cause hyperglycemia and hypeterTAG and may have a small effect on fat distribution. However, these effects have not been seen with loop diuretics (eg, furosemide).

d. unlike glucocorticoids, NSAID doesn't cause this shit

e. PPI are use to reduce gastric acid secretion in patients with peptic ulcers or GERD, which can cause hypomagnesemia and increased osteoporosis

f. thyroperoxidase inhibitor (eg, methimazole and propylthiouracil) are used to treat hyperthyroidism. Common side effects are bone marrow suppression (eg, anemia and agranulocytosis)
NF-kB is a family of transcription factors that perform critical role in the immune response to infection and inflammation. In inflammatory cells, NF-kB is normally present in a later, inactive state bound to its inhibitor, IkB.

When extracellular signal, such as binding of bacterial antigens to a toll like receptor, causes activation of IkB kinase. This results in ubiquitination and subsequent destruction of IkB with release of free NF-kB. Once free, NF-kB enters the nucleus and promotes the synthesis of number of inflammatory proteins such as cytokines, acute phase reactions, cell adhesion molecules, and leukocyte related growth factors. The inflammatory cascade is self-limiting as NF-kB also stimulates the transcription of more IkB, ultimately rebinding the freed NF-kB.

a/e: G-CSF is the principal protein the stimulates the production and relate of neutrophils from bone marrow. TNF-alpha plays a role in response to infection by increasing neutrophil chemotaxis and stimulating macrophage phagocytosis. Although nfkB up regulates transcription of G-csf AND tnf-A, IKB DEGRADATION IS NOT DIRECTLY INVOLVED IN ACTIVATION OF THESE FACTORS

B. JAK2 is a TK involved in the signaling pathway for myeloproliferation. Constituent activation of JAK 2 is associated with polycythemia vera, essential thrombocytosis and myelofibrosis. It doesn't play a major role in the immune response to infection

d. although transforming growth factor -beta (TGF-beta) plays a role in immune response and is triggered by inflammatory pathways, it is complexed to TGF-beta binding protein and latency associated peptide not IkB.
Kid has complete AV canal defect, most common type of cardiac defect seen in Down syndrome.

Failure of endocardial cushion results in osmium primum atrial defect: a ventricular septal defect; and a single AV valve.

Significant left-to-right shunting an dAV valve reguregurgitation lead to excessive pulmonary blood flow and symptoms of heart failure (eg, tachypnea, poor feeding)

Auscultatory findings of AV valve regurgitation (holsystolic, best heard at the apex) and increased pulmonary venous return (mid diastolic rumba) are characteristic.

a. DiGorge is characterized by thyme aplasia (T cell def) and hypoparathyroidism (hypocalcemia). it is associated with tetralogy of Fallot, trunks arterioles and transposition of the great arteries.

c. Marfan syndrome (fibrillin-1 mutation) is associated with cystic medial necrosis of the aorta, which may result in dissecting aortic aneurysms and aortic valve regurgitation. Mitral valve prolapse is also common, but septal defects are not

d. mutations of frataxin, a mitochondrial protein important in iron homeostasis and respiratory function, cause Freidrecih ataxia. It is characterized by spinocerebellar degernation and is associated with hypertrophic cardiomyopathy, but not septal defects.

e. mutations in tubers and harmartin are seen in tuberous sclerosis. These patients may develop cardiac rhabdomyomas in ventricular walls and AV valves, cutaneous angiofibromas (adenoma sebaceous), CNS hamartomas and renal cysts.

f. turner is associated with bicuspid aortic valve (most common cardiac lesion) and coarctation of the aorta.
Most inhaled anesthetics, barbiturates, and bentos achieve CNS depression by influencing GABA receptors and increasing the inhibitory action of GABA. Inhaled anesthetics have also been shown to affect potassium channels in the neuronal membranes and lock them in the state of hyperpolariation. They may also affect nicotinic glycine receptors. Apart from their desired action on CNS, inflation has affect on almost all organ systems of the body:
1. CVS: decrease in CO and increase in atrial and ventricular pressures. Hypotension associated with fluorinated anesthetics is a result of decrease in CO.
2. Respiratory: all inflation anesthetics, except NO, are respiratory depressants. They decrease tidal volume and minute ventilation and cause hypercapnia. Another undesirable effect is suppression of mucciliary clearance, which may predispose to postoperative atelectasis. Halothane and sevoflurane have bronchodilation properties and are preferred in patients with asthma.
3. in the brain, fluorinated anesthetics decrease vascular resistance and lead to an increase in cerebral blood flow. It is an undesirable effect because it causes increased intracranial pressure.
4. in kidneys, inhaled anesthetics decrease GFR, increase renal vascular resistance and decrease RPF
5. Fluorinated anesthetics decrease hepatic blood flow.

a/b: renal function in general anesthesia is characterized by decrease if GFR and decrease in RPF

c. fluorinated anesthetics are myocardial depressants. They decrease CO which leads to hypotension

d. fluorinated anesthetic decrease hepatic blood flow.
Isolation of the fastidious N. gonorrhoeae requires a selective medium the twill inhibit the growth of the other bacteria normally present in the oral cavity.

A chocolate agar-based medium containing various antibiotics, the Thayer-Martin medium (and modified Thayer-Martin medium) is commonly used to isolate Neisseria from clinical specimens. The commonly used antibiotics are:
-vancomycin to inhibit gram-positive bacteria
-colistin (i.e., polymyxin) to inhibit gram negative bacteria (commensal Tessera species but not N. meningitides or N. gonorrhea)
-Nystatin to inhibit yeast
-TMP to inhibit the Proteus species

a. E. coli is gram-neg rod which is inhibited by colistin (i.e., polymyxin) and TMP. In addition, it is not associated with pharyngitis however it is the most common causes of gram neg sepsis

b. S. pyogenes (i.e., group A strep_ is an important pharyngeal pathogen because it can cause pharyngitis that if left untreated, can lead to rheumatic fever. Strep is gram positive is being taken care of by Vancomycin in the Thayer-Martin selective culture

C. S. pneumoniae is being inhibited by vancomycin. It is not an important cause of pharyngitis but it is an important cause of meningitis and community-acquired pneumonia in adults.

d. K. pneumoniae is gram neg rod that is being taken care of by colistin (ie. polymyxin) and TMP. It is not associated with pharyngitis but classically causes severe pneumonia in alcoholic or otherwise severely disabled patients. It also causes nosocomial sepsis and UTIs. It is a part of the oropharyngeal normal flora and characteristically causes pulmonary infection following aspiration.

f. C. diph was historically important causes of pharyngitis in the US prior to the introduction of the diphtheria-pertussis-tetanus vaccine. Children clinically present with fever and sore throat, with an evident pseudomembrane. It is a gram positive organism inhibited by vancomycin.
Genetic information flows from DNA to RNA to proteins. Post uekaryotic DNA sequences consist of coding exon, noncoding introns, and 2 promoter regions ( the CAAT box and the TATA box).

The CAAt box is located 70-80 bases upstream of the beginning (5' end) of the coding region, and the TATA box is located 25 bases upstream from the beginning of the coding region.

Gene transcription begins when RNA polymerase II attaches to one of the promoter regions in a process that requires general transcription factors. A DNA enhancer region then binds activator proteins that associate with transcription factors and RNA polymerase II at the promoter, thereby increasing gene expression. Although promoters are not directly translated into protein, promoter mutations can cause abnormal gene expression by altering ability of RNA polymerase II and transcription factors to bind.

a. DNa methylation is part of the epigenetic code. This process sis carried out by DNA methyltransferases and serves to silence the genes it affects

b. folding of a formed polypeptide into its secondary adntertiary structures is entirely spontaneous and is determined by the amino acid sequence in the protein's primary structure. heat shock proteins assist in the spontaneous refolding of proteins.

c. Posttranscriptional RNA splicing is facilitated by snRNPs that remove introns from heterogeneous nuclear RNA (hnRNA) containing GU at the 5' splice site and AG at the 3' splice site

d. the TATA box only participates in the initiation of transcription. The addition of nucleotides to th forming RNA molecule (RNA elongation) continues until RNA polymerase II encounters a termination signal.

f. In eukaryotes, translation initiation requires both ribosomal subunits (60S and 40S) with their associated rRNA, mRNA, initiation factors, initiator tRNA charged with methionine, and GTP. The assembled ribosome then recognizes the AUG start codon on mRNA to being the process
Contact dermatitis, granulomatous inflammation, the tuberculin skin test and the Candida extract skin reaction are all examples of delayed type hypersensitivity reactions (DTH).

The cells that mediate DTH are T-lymphocytes. This reactions don't involve antibody or complement. These actions are referred to as "delayed' responses because, unlike reactions mediated by antibody that occurs MINUTES after antigen exposure (i.e.. ABO blood group incompatibility, hyper acute rejection, erythroblastosis fettles), delayed reaction occur one to two days following antigen exposure (this is why you need to wait 48 to 72 hours for your annual PPD test to be read).

In DTH antigen is taken up by the dendritic cells and presented to to CD4 Th-lymphocytes on MHC Class II molecules. These stimulated Th-lymphocytes (usually of the TH1 lineage) then release interferon-g, which acts to stimulate and recruit macrophages leading to a monocytic infiltration of the area where the antigen is introduced. This is also responsible for the "walling-off" of M. tuberculosis infection in the lung and other forms of granulators inflammation with monicytic and giant cell infiltrates.

b. B-lymphocytes are the major effector cells in the humoral immunity because they synthesize and secrete immunoglobulin. Hypersensitivity reactions mediated by antibodies include Type I (IgE mediated, i.e.. asthma, anaphylaxis), TYPE II (antibody mediated, i.e. ABO incompatibility hemolysis) and Type III (immune complex (ie. PSGN). B-lymphcoytes are stimulated by IL03 release from the TH2 subset of Th lymphocytes.

c. Neutrophils are the primary phagocytes of the innate immune system and do not play a role in any of the four immune hypersensitivity reactions. Neutrophils are produced in the bone marrow and have a multi lobed nucleus. They are usually the first leukocytes to arrive at the site of inflammation and they are able to ingest and kill organisms by enzymatic and oxidative burst pathways. their presence in increased numbers in the blood is indicative of infection, especially with predominance of band forms referred to as a "left shift," but their numbers in the blood can be falsely elevated in a patient who has recently been administered corticosteroids. This effect of corticosteroids on the leukocyte count is attributable to the fact that corticosteroids cause" demmargination" (release from vascular walls) of these cells.

d. eosinophils are phagocytic cells that are believed to play a role in the defense against parasitic organisms. These cells are present in small numbers in the blood stream and are believed to play a role in the pathogenesis of asthma as they are often found in increased numbers in the bronchial mucosa of patients with this illness, but asthma is primarily a Type I hypersensitivity response.

e. Mast cells are granulocytes that exist in many tissues in the body and are primary mediators of the clinical effects of allergic reactions. They express Fc receptors for IgE, and IgE acts as the primary antigen receptor for these cells. When two membrane-bound molecules of IgE bind the same antigen, "cross-linking" occurs that directly leads to mast cell degranulation and release of mast cell granular contents such as histamine and heparin. Disorders of mast cells include urticaria pigments nd systemic mastocytosis.
During the first encounter with an antigen (allergen), antigen-presenting cells such as macrophages, B lymph and dendritic cells take up and process the antigen and display it in associated with MHC II molecules.

T-cells become activated when they detect the MHC II-associated antigen, and differentiate into Th1 or Th2 subsets.

Th2 lymph promote the humoral immune response by secreting IL-4 and IL-5:

Some activated B-cels transform into plasma cells that produce antigen-specific IgM (primary response). The majority of activated B-cells proliferate in the germinal centers of lymph nodes an transform into memory cells. Antibody switching then allows B-cells to secrete other amor subtypes of immunoglobulin such as IgG, A and E during subsequent encounters with the antigen (secondary response).

IL-4 and IL-5 are the main cytokines that stimulate the growth and differentiation of B-lymphcoytes after exposure to antigen.
-Specifically, IL-4 is responsible for B-cell growth and isotype switching. IL-4 stimulates secretion of IgE and predisposes to type I (immediate) hypersensitivity reactions. It also stimulates differentiation of TH0 (naive) T-helpcer cells into Th2 helpers, thus increasing the Th2 subpopulation and the stimulus for the humoral immune response.
-IL-5 is responsible for B-cell differentiation; it stimulates IgA production and eosinophil activity and is important for host defense against parasitic infections.

a. IL-1 is made by macrophages. It activates naive TH0 lymphocytes and promotes their differentiation into Th1 and Th2 subpopulation. IL-1 is also an endogenous pyrogen.

b. IL-2 is the first interleukin produced by T-cells after contact with antigen. It is secreted mainly by Th1 cells and stimulates development of CD4 T-helper cells, CD8+ cytotoxic cells and B cells.

c. IL-3 stimulates growth and differentiation of bone marrow stem cells and is produced by T-helper cells.

e. IL-10 helps regulate the balance between Th1 and Th2 subpopulations of T-helper cells. It is produced by Th2 lymphocytes and inhibits synthesis of interferon-g leading to decrease in the Th1 subpopulation

f. IL-12 is synthesized by macrophages and stimulates growth and development of the Th1 subpopulation of T-helper cells.
This patient has typical symptoms of hypoglycemia (eg, disorientation, sweating, tremors, palpitations), which are relieved by intake of glucose. the 3 most important predisposing factors for hypoglycemia in patients with type 1 dm are excessive insulin dose, inadequate food intake, and physical activity/exercise.

GLUT-4 expressed on skeletal muscle cells are translocated to cell membrane and transverse tubules (deep invaginations in the cell membrane) in response to insulin. It translocation also occurs during muscle contraction by insulin independent mechanism, which is mediated by several cellular factors, including AMP-activated kinase, nitric oxide, and calcium calmodulin activated protein kinase.

In normal individuals, over hypoglycemia doesn't occur with exercise because a drop in blood glucose will stop insulin release from the beta cells and counter-regulatory hormones (eg, glucagon) will increase endogenous glucose production via glycogenolsyis and gluconeogenesis. However, patients taking exogenous insulin are vulnerable to exercise induced hypoglycemia as insulin will continue to be released from the injection site despite falling glucose levels. In addition, strenuous exercise may cause changes in skin perfusion that can lead to increased insulin absorption (especially if the insulin is injected into an exercising limb rather than the abdominal area).

b/c/d. infection, pain and sleep deprivation tend to cause hyper-rather than hypoglycemia. Stressful situations increase catecholamine release, which raises glucose by decreasing pancreatic insulin secretion and by increasing glycogenolysis and gluconeogeneiss.

e. weight gain is associated with insulin resistance insulin-treated patients who gain weight usually develop hyperglycemia and require increased doses of insulin to maintain control of glucose
this patient's clinical findings are highly suggestive of Klinefelter syndrome, the most common cause of male hypogonadism.

In klinefelter syndrome, progressive destruction and hyalinization of the seminiferous tubules cause the testes to be small and firm.
-Sertoli cells are damaged causing inhibin levels to be low
-Leydig cells are usually dysfunctional as well thus patient will have low level of testosterone
-The loss of feedback leads to elevated FSH and LH. Patients can also develop high estrogen levels and gynecomastia d/t increased aromatase activity (stipulated by gonadotropin excess).

Most patients with classic (47, XXY) Liefelter syndrome have azoospermia and are infertile, but those with mosaic variants may have variable degrees of spermatogenesis.

a. Low LH and FSH, along with low testosterone, are consistent with hypogonadotropic (central) hypogonadism, which can result form damage to the hypothalamus or pituitary gland The congenital def of GnRH, called Kallmann syndrome, is generally associated with anosmia. In addition, hypogonadotropic hypogonadism is less likely to cause gynecomastia as the decrease in gonadotropins reduces aromatase activity.

b. patient with normal hormonal profile but lacking sperm may have an obstruction somewhere along the path from the testes to the seminal fluid. For example, this occurs with congenital absence of the vas deferent in cystic fibrosis.

c. decreases LH , normal FSH and elevated testosterone in setting of a low sperm count is suggestive of exogenous testosterone use. High androgen levels suppress LH secretion,d decreasing endogenous testosterone production. Despite the high circulating levels of exogenous androgens, these patients have a low sperm count as local androgen contractions in the seminiferous tubules are suboptimal for spermatogenesis. Over time, this leads to atrophy of the seminiferous tubules and a decrease in testicular size.

e. normal LH and testosterone, elevated FSH and a low perm count can be seen in patients with cryptorchidism. In this condition, the seminiferous tubules are damaged (resulting in elevated FSH levels) and the interstitial Leydig cells are preserved (maintaining normal LH and testosterone levels).
Patient has abetalipoproteinemia, a disease caused by the impaired formation of apolipoprotein B containing lipoprotein.

Dietary lipids are normally processed in small-bowel enterocytes and secreted as chylomicrons; endogenously produced lipids are secreted from the liver hepatocytes as VLDL. Chylomicron and VLDL has apoB-48 and apoB-100, respectively. During the synthesis of api-b-containing lipoproteins, microsomal triglyceride transfer protein functions as a chaperone protein necessary for proper folding of apoB and also participates in the transfer of lipids to newly formed chylomicrons and VLDL particles.

this is the most commonly caused by an AR, loss-of-funcito mutation int he MTP gene. It manifests during the first year of life with symptoms of malabsorption (eg, abdominal distention, foul-smelling stool). Lab shows very low plasma TAGs and cholesterol levels, and chylomicrons, VLDLs and apoB are entirely absent form the blood. Poor lipid absorption auses deficiency of fat soluble (particularly vitamin E) and essential fatty acids. This results in RBC with abnormal membrane and thorny projections called acanthocytes as well as multiple neurologic abnormalities (eg, progressive ataxia, retinitis pigmentosa)

b. celiac biopsy will have atrophy and blunting of the villi in celiac disease. Chronic inflammatory infiltrate of the lamina proper is also present.

c/e/g: no abnormalities are found in LM of the SI in chronic pancreatitis, Zollinger-Ellison syndrome or lactase def.

d. LM of Crohn's shows chronic inflammation of all layers of the intestinal wall and noncaseating granulomas

f. Whipple has distended macrophages in the lamina propria of the SI> Macrophages contain PAS-positive and diastase-resistant granules and rod-shaped T. whippelii bacilli.
Adverse effects of succinylcholine
1. malignant hyperthermia (especially with halothane) in genetically susceptible patients
2. severe hyperkalmeia in patients with burns, myopathies, crush injuries and denervation
3. bradycardia from parasympathetic stimulation or tachycardia from sympathetic effects.

Succinylcholine is a depolarizing NMJ blocking agent. Like Ach it attaches to the nicotinic acetylcholine receptor (nAChR) and depolarizes the euromuscular end plate. Unlike Ach, succinylcholine is not degraded by acetylcholinesterase, resulting in continuous stimulation of the endplate (reflected by intimal transient fasciculations).

However, the Na channels surrounding the end plate rapidly become inactivated and cannot reopen until the end plate is depolarized. Thus, succinylcholine-induced depolarization remains isolated to the endplate, resulting in development of flaccid paralysis (phase 1 block).

Eventually, with continued administration of succinylcholine, the continuous depolarization of the endplate gives way to gradual depolarization as the nAChR becomes desensitized to the effects of succinylcholine. This in termed phase II block and is similar to non-depolarizing block.

Because the nAChR is a nonselective cation channel, its opening not only allows Na influx but also K release. Exaggerated hyperkalemia nd life-threatening arrhythmias can occur in patients with crush or burn injuries, denervating injuries or diseases (eg, quadriplegia and Guillain-Barre syndrome), and myopathies. These pathogloic states cause up regulation of muscle nAChRs and and/or rhabdomyolysis, which can result in the release of large amount son K when succinylcholine is administered. IN these patients, non-depolarizing agents such as vecuronium and rocuronium are better choices.

a. atracurium is a nondepolazizing NMJ blocking agent releases histamine and can produce a fall in blood pressure, flushing and bronchoconstricition. It is also metabolized to laudanosine, which can provoke seizures.

b. baclofen is a muscle relaxant that affects GABAb receptors at the level of the spinal cord

c. dantrolene is a muscle relaxant effective in malignant hyperthermia. It acts on ryanodine receptors on the sarcoplasmic reticulum and prevents release of Calcium in to the cytoplasm of muscle fibers.
Heparin is the most important cause of thrombocytopenia in hospitalized patients. Occurrence of HIT (heparin induced thrombocytopenia) is much more common with use of unfractonated heparin compared to low molecular weight heparin. HIT more commonly leads to paradoxical thrombosis rather than bleeding. HIT is a serious disorder caused by antibodies to heparin and platelet factor IV.

Direct thrombin inhibitor (huridin, lepirudin and argatroban) do not require antithrombin-III for their actions and are drugs of choice in treatment of HIT. Patients with HIT need ongoing anticoagulation d/t the presence of, or possibility of thrombosis. Upon clinical suspicion of HIT, the most important initial step in treatment is to stop all forms of heparin.

b. Warfarin inhibits vitamin K dependent y-carboxylation of glutamic acid residues of clotting factors II, VII, IX and X.

c/d/e: platelet plug formation involves there critical steps: adhesion, aggregation and release. Drugs that inhibit platelet aggregation work by different mechanism.
-Aspirin irreversibly acetylates platelet COX-1 leading to decreased formation of thromboxane. This drug is sued for primary and secondary prevention of MI and strokes
-Ticlopidine and clopidogrel inhibit ADP mediated platelet aggregation. They are useful following percutaneous coronary intervention (PCI), and for treatment of unstable angina and non-Q wave MI.
-Dipyridamole and cilostazol inhibit platelet aggregation by inhibits phosphodiesterase activity and increasing cAMP.
-Glycoprotein IIb?IIIa inhibitors inhibit biding of platelet glycoprotein IIb/IIIa with fibrinogen and fibronectin. The glycoprotein IIb/IIIa inhibitors abciximab, eptifibatide and tirofiban are approved for use following percutaneous interveion (PCI) in acute coronary syndrome.
The unit in this study is population not individuals. This is consistent with an ecological study, in which the frequency of a given characteristic (eg, vitamin D intake) and a given outcome (eg, multiple sclerosis (MS)) are studied using population date. Ecological studies are useful to generate hypotheses but should not be used to make conclusion regarding individuals within these populations.

a/b: case control and cohort studies would start with individuals rather than populations.
-In case-control studies, the odds of exposure to a certain characteristic (eg, high or low vitamin D intake) is compared between affected individuals (eg, patients with MS) and unaffected individuals who serve as controls.
-In cohort studies, individuals (with and without different exposures such as high or low vitamin D intake) are followed over time to determine incidence of disease of interest (such as MS).

c: cross-sectional surveys would also evaluate the exposures and outcomes of interest in individuals (not populations) at a given point in time ("snapshot").

e. nested case control designs start with cohort studies in which participants are followed over time,a nd those participants who develop an outcome of interest become cases for a case-control study.

f. qualitative studies are focused discussion groups, interviews (structured and semi-structured), and other anthropologic techniques to obtain narrative information that can be crucial in explaining quantitative results.

g. randomized controlled trials enroll individuals who will be randomly assigned into a treatment group or a control group. the groups differ only in terms of intervention (treatment) of interest).

h. systematic reviews and meta-analyses take several studies (with an emphasis on high-quality randomized controlled studies) and attempt to group the results to obtain a pooled effect estimate .
Focal dystonia is a localized uncontrollable muscle contraction causing pain or discomfort as well as physical deformity in some cases.

Local injection of botulinum toxin type B into the dystonic SCM results in muscular relaxation because toxin prevents presynaptic release of ACh, the NT responsible for muscle contraction, from the nerve terminal at the NMJ.

This effect is temporary, however, because regeneration of the nerve terminal eventually occurs. (this process takes approximately three months.) For this reason, therapeutic botulinum toxin injections must be repeated when the effects begin to diminish.

Botulinum toxin can also be used cosmetically to reduce the appearance of glabellar and other facial wrinkles. It is also used to relax the lower esophageal sphincter in esophageal achalasia, to treat the muscle spasms of MS and Parkinson's disease, and for other conditions resulting form involuntary muscle contraction.

C. botulinum is a gram positive spore-forming anaerobic bacillus that synthesizes its point neurotoxins intracellularly and releases them by autolysis.

a. antiphagocytic capsule is the primary virulence factor for S. pneumonia, H. influenza and Neisseria bacteria.

b. hyper variable pili are characteristics of Neisseria meningitides and N. gonorrhoeae.

c. S. aureus has an IgG-binding outer membrane protein, the Protein A virulence factor. Protein A binds to the Fc portions of IgG molecules thereby preventing opsonization, phagocytosis and complement fixation.

d. intracellular polyphosphate granules are characteristics of C. diph. Granules within the cytoplasm are evident with methylene blue staining.
This patient has appendicitis, which can cause both visceral (dull,non-localized) and somatic (severe, well-localized) abdominal pain.

Visceral abdominal pain is most often d/t luminal distention and stretching of smooth muscle and is carried by general visceral afferent fibers of the autonomic nervous system. The pain typically occurs int he midline region and is poorly localized and of a dull, constant, or cramping quality. Patients can also develop nausea, vomiting, or sweating d/t the autonomic stimulation.

Somatic pain is usually d/t irritation of the parietal peritoneum and is well localized, more severe, and worsened with deep inspiration or pushing on the abdominal wall.

the afferent pain fires for the appendix , proximal colon and overlying visceral peritoneum cross through the superior mesenteric plexus and enter the spinal cord at the t10 level to produce vague, referred pain at the umbilicus. As the appendix becomes more inflamed, it irritates the parietal peritoneum and abdominal wall and causes a more severe somatic pain that shifts from the umbilical region to McBurney point (two-third of the distance from the umbilicus to the anterior superior iliac spine). The abdominal wall becomes very sensitive to gentle pressure or sudden release of deep pressure (rebound tenderness).

b/c: the appendix is usually 2 cm beneath the ileocecal valve in the RLQ. Depending on its orientation, there can be additional clinical findings. An inflamed appendix lying against the right obturator interns muscle can cause right lower quadrant pain with internal rotation of the right hip. If the inflamed appendix lies against the right tpsoas muscle, there can be pain with hip extension.

d. the cecum is innervated by the superior mesenteric plexus and has only visceral sensation.

e. patients with retrocelcal appendix may not have significant right lower quadrant tenderness,as the inflamed appendix doesn't contact the anterior parietal peritoneum and the cecum (distended with gas) acts as a cushion that blocks the examiner's hand.
This patient has obstructive sleep apnea (OSA), which is characterized by recurrent obstruction of the upper airway during sleep; each nocturnal episode of reduced ventilation causes transient hypercapnia and hypoxemia. These blood gas derangements result in reflexive systemic and pulmonary vasoconstriction, endothelial dysfunction, abnormal venous return and CO, and sympathetic cardiac stimulation.

Prolonged, untreated OSA can cause pulmonary HTN and RH failure. Most patients with OSA will develop systemic hypertension d/t chronic sympathetic stimulation and elevated plasma NE levels Patients also lose the normal diurnal variation in blood pressure. Other CVS complications of OSA include
-afib (and other arrhythmias)
-sudden cardiac death

a. acquired bronchiectasis may be seen in patients with recurrent infection, impaired drainage (eg cystic fibrosis ), airway obstruction (eg, foreign body aspiration), or inadequate host defense (eg, hypogammaglobulinmemia).

b. systemic HTN, as seen in OSA, can lead to mild-to moderate left ventricular hypertrophy and impaired systolic and diastolic function. In contrast, hypertrophic cardiomyopathy is an autosomal dominant disease of the cardiac sarcomere characterized by severe myocardial hypertrophy. It is not associated with HTN or SOA

c. laryngeal carcinoma is associated with cigarette smoking and heavy alcohol use

d. like OSA< narcolepsy can also cause daytime drowsiness. However, narcolepsy is also associated with cataplexy (sudden loss of muscle tone), sleep attacks, sleep paralysis, and hypnagogic hallucinations. OSA is not a risk factor for narcolepsy.
Causes of ostemelitis:

Childhood age: hematogenous seeing during an episode of bacteremia. Most frequent pathogen is S. aureus. Typical location is long bones.

Sickle cell disease: Hematogenous seeding to infarcted bone. Most frequent pathogens are Salmonella and S. aureus. Typical location is long bones.

Post disease: hematogenous seeding from lungs. Most frequent pathogen is mycobacterium tuberculosis. Typical location vertebrae.

DM: contiguous spread from infected foot ulcer. Most frequent path is poly micro affecting the bones of the feet

Recumbent patients with impaired mobility. Contiguous spread from pressure sores. Most frequent pathogen polymicrobial affecting the sacrum and heels

Recent trauma or orthopedic surgery. Direct inoculation. Polymicrobial and location is variable.

Osteomyelitis is an infection of the bone and bone marrow that occurs by 1 of 3 mechanisms:
1. hematogenous seeding d/t an episode of bacteremia
2. spread from a contiguous focus infection, as occurs in an infected diabetic foot wound
3. direct inoculation of bone, such as with a compound fracture

Hematogenous osteomyelitis occurs predominantly in children and most frequently affects the long bones the tibia, fibula, and femur are most often involved. Adults who develop the condone are more likely to have vertebral involvement and frequently have a predisposition to bacteremia d/t risk factors such as IV drug abuse or indwelling vascular catheters.

S. aureus is implicated in most cases of acute hematogenous osteomyelitis in otherwise healthy children

a. enterococcus faecalis causes a variety of infections, including endocarditis, meningitis, and urinary tract infections. Enterococcus can cause vertebral osteomyelitis after a recent UTI via bacteremic spread.

b. moraxella catarrhalis is part of the normal flora of the URT. It causes otitis media and sinusitis in healthy individuals and is frequently responsible for causing exacerbation of COPD.

d. S. epidermis is ubiquitous in nature and is commonly isolated in cultures as contaminant. However,r S. epidermis can also be pathogenic, colonizing IV catheters and the foreign bodies such as prosthetic heart valves and orthopedic hardware, leading to bacteremia and sepsis.

e. S. agalactiae (group B strep) frequently colonizes the GI and urogenital tracts. Infants porin vaginally to colonized mothers can develop serious neonatal infections, including sepsis, pneumonia, and meningitis. For this reason, pregnant women testing positive for group B strep are treated with antibiotic prophylaxis during labor and delivery.

f. s. pneumoniae is the most common etiologic agent of community acquired pneumonia. It also causes otitis media in children, sinusitis, meningitis and sepsis

g. S. aureus, S. pyogenes (group A strep) is the second most common cause of hematogenous osteomyelitis in children. Group A strep are also responsible for strep pharyngitis and skin infections such as impetigo and necrotizing fasciitis.
After transcription, the preliminary, unprocessed mRNA is known as precursor mRNA, or heterogenous nuclear RNA (hnRNA). Eukaryotic pre-mRNA undergoes significant post transcriptional processing before leaving the nucleus, including 5' capping, poly A tail addition, and intron splicing.

Once mRNA is finalized, it leaves the nucleus bound to specific packaging proteins. Upon entering the cytoplasm, these mRNA complexes often associated with ribosome to undergo translation. However, certain mRNA sequences instead associate with proteins that are found in P bodies.

P bodies are distinct foci within eukaryotic cells that are involved in MRNA regulation and turnover. They play a fundamental role in translation repression and mRNA decay, and captain numerous proteins including gRNA exonuycleases, mRNA recapping enzymes, and constituents involved in mRNA quality control and microRNA-induced mRNA silencing. P bodies also seem to function as a form of mRNA storage, as certain mRNAs are incorporated into P bodies only to be alter related and utilized for protein translation.

a/b: The 4' end of all mRNA is capped with a 7-methylguanosine residue by a unique 5' to 5' linkage, which occurs in two stages. The first step is addition of guanine triphosphate to the 5' end of mRNA in reaction catalyzed by guanylytransferase. Methylation of the guanosine cap is then catalyzed by guanine-7-methyltransferase. Capping of the precursor RNA occurs in the nucleus as the ran is being transcribed. This methylated cap protect mRNA from degradation by cellular exonuclease, and allows it to exit the nucleus.

c. mRNA is polyadenylated at the 3' end by the polyadenylate polymerase complex, which recognizes a specific sequence (AAUAAA), cleaves the pre-mRNA molecule a few residues downstream from the sequence, and then adds a stretch of 20-250 adenine residue called the poly A tail. The addition of the poly A tail occurs before th emRNA exits the nucleus. IN the cytosol, th poly A tail is gradually shortened, eventually leading to mRNA degradation.

d/e: since pre-mRNA contains both introns and exon, and only exon code for proteins, introns must be excised before translation through process known as splicing. Splicing of pre-mRNA occurs within the nucleus and is facilitated by interaction of pre-mRNA with small ribonucleoprotein particles called snRNPs (or "slurps" for short).
Ingeneticially normal (46, XX) females, on eX chromosome is normally randomly deactivated each cell during early embryonic development. X-incativaiton (lionization) is maintained across cell division, resulting in clusters of cells throughout the body that express either the maternal or paternal X chromosome.

this mosaic pattern of X-chromosome expression generally prevents X-linked recessive conditions from naifestating in female carriers. However, in rare cases, skewed lionization (uneven inactivation of maternal/paternal X chromosome d/t chance alone may result in females developing an X-linked recessive condition (eg, classic hemophilia).

The process of lionization converts the inactive X chromosome into condense heterochromatin, which can be identified on microscopy as a compact by at the periphery of nucleus (Barr body). Heterochromatin consist of heavily methylated DNa (eg, cytosine converted to methyl cytosine) and deacetxyalted histones, which cause it to have a low level of transcriptional activity.

A small proportion of genes rain transcriptionally active on the inactivated X chromosome. For this reason, inheritance of an abnormal number of X chromosomes can cause clinical manifestations d/t a gene dosage effect, as seen in Turner (45, XO) and Klinefelter (47, XXY) syndromes.

a. during DNA replication, positive supercoiling occurs in the region ahead of the replication fork and must be removed for DNA replication to proceed. Topoisomerase's reduce DNA supercoiling by nicking the DNa strands, introducing negative coiling, and relegating the strands.

b. double strand DNA breakage can occur following exposure to ionizing radiation. Compared to single strand breakage, double stranded breaks are more prone to result in faulty repair, leading to mutations, malignancy or cell death

d. repair mismatched bases occurs throughout the genome during DNa replication. Impaired mismatch repair is associated with hereditary non polyposis colorectal cancer.
selective estrogen receptor modulators

Drugs: tamoxifen/raloxifene
MOA: competitive inhibitor of estrogen binding. Mixed agonist/antagonist action
Indications: prevention of breast cancer in high-risk patients.
-Tamoxifen: adjacent treatment of breast cancer
-Raloxifene: postmenopausal osteoporosis
A/Es: hot flashes, venous thromboembolism and endometrial hyeprplaisai and carcinoma (w/ tamoxifen only).

Estrogen plays a critical role in bone and reproductive organs, including skeletal homeostasis and proliferation of the endometrium. Because estrogen decreases bone resorption, estrogen def in postmenopausal women increase the risk of osteoporosis. In the uterus, unopposed estrogen exposure (eg, estradiol therapy) canc cause excessive endometrial proliferation resulting in endometrial hyperplasia and cancer.

Selective estrogen receptor modulators (eg, raloxifine, tamoxifen) are non steroidal compounds that bind to estrogen receptor and exhibit estrogen antagonist and agonist properties in a tissue specific manner.

RALOXIFENE: excellent choice for prevention of breast cancer and osteoporosis because it has estrogen antagonistic activity on breast. Furthermore, raloxifine has estrogen antagonistic activity on uterus and doesn't increase the risk of endometrial cancer.

TAMOXIFEN: has a strong estrogen antagonist activity in the brest and is used in the treatment of estrogen receptor positive breast cancer. Although tamoxifen produces estrogen-like effects on bone and can reduce the risk of osteoporosis, it agonist activity on the uterus (eg, increased risk of endometrial yperplasia/cancer) limits its potential in osteoporosis management.

a. alendronate is a synthetic bisphosphonate. As a bone resorption inhibitor it prevents and treats osteoporosis in postmenopausal women. Bisphosphonates do not protect against breast cancer.

c. leuprolide is a GnRH analog with estrogen agonist properties when administered in pulsatile manner and antagonist properties when administered continuously. Its use as an agonist increases estrogen and protects against osteoporosis. However, it use as an antagonist decreases estrogen, protecting against estrogen receptor psotivie breast cancer but not osteoporosis.

d. oral medroxyprogesterone reduces the incidence of endometrial hyperplasia and the risk of endometrial carcinoma in postmenopausal women on estrogen replacement therapy. Prolonged use of intramuscular medroxyprogesterone as a contraceptive is associated with decreased bone mineral density.
The atherosclerotic occlusion of a coronary artery develops very slowly over time, there can be compensation by the development of arterial collaterals around the point of occlusion. The pressure gradient across the stenotic region facilitates blood flow through the small anastomotic vessels, which progressively dilate. The collateral circulation can provide flow to the hypo perfused areas distal to the point of occlusion. In this case, the patient likely developed collaterals from the right coronary artery to distal vessels normally perfused by the LAD

a. when the fibrous cap overlying a coronary atherosclerotic plaque is thin, the plaque is unstable and predisposed to ulceration, fissuring, or rupture. Rupture of an atherosclerotic plaque can lead to overlying thrombosis and acute coronary occlusion, which resultant ischemic myocardial injury. This process occurs too quickly to be compensated by the development of new arterial collaterals.

b. atherosclerotic rookery plaques with a rich lipid core are more prone to plaque rupture, and thus more lily to cause an acute ischemic coronary syndrome d/t superimposed thrombosis.

c. activated macrophages in an atheroma contribute to collagen degradation by secreting metalloproteinases. When there is a high degree of intimal inflammation, release of these metalloproteinases is increased, which can destabilize the mechanical integrity of the plaque, Statins (HMG Co-A reductase inhibitors) decrease this inflammation and are useful in acute coronary syndrome to stabilize the plaque,

e. the total coronary artery calcium content correlates modestly with the coronary artery atherosclerotic plaque burden. Thus, patients with advanced coronary calcification may be at increased risk fro ischemic myocardial injury. However, the calcium content of an individual plaque is not correlated with the probability of rupture or degree of plaque stability. Thus the presence of intra-plaque calcium could be consistent with either an acute contrary syndrome or with gradual occlusion without myocardial necrosis.

f. An postal location of a coronary artery plaque would not give a finished tendency to cause ischemic myocardial injury. IN fact, it might promote such injury by compromising blood flow to a larger area of the myocardium. However a more important determinant of whether or not coronary plaque causes myocardial necoriss is the rate of arterial occlusion. A slowly progressive postal obstruction would not necessarily prevent the development of an adequate collateral circulation
This patient has cerebrovascular and coronary atherosclerosis ( causing transient ischemic attacks and angina), which increases the risk of atherosclerosis in other organ systems. Atherosclerosis involving renal arteries can cause bilateral renal artery stenosis (RAS) in such patients.

Reduced renal blood flow (eg, from dehydration or RAS) decreases GFR d/t fall in hydrostatic pressure. This stimulates renin production, which leads to angiotensin II formation.

Angiotensin II causes systemic vasoconstriction with a resultant rise in BP.

In the kidney, angiotensin II preferentially constricts the efferent arteriole. Blocked of this response by ACE inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) causes the filtration pressure to fall, thereby reducing GFR. In unilateral RAS, the normal kidney compensates for decreased GFR< and overall creatinine clearance is maintained. However, patients with bilateral RAS may develop acute renal failure. Therefore, renal function should be monitored closely after starting gACEI/ARBs in patients with evidence of diffuse atherosclerosis.

a/e: ACEI/ARBs have multiple cardiac benefits. They cause peripheral vasodilation that reduces after load. This decreases the contractile force needed to maintain CO, reducing myocardial oxygen demand. These drugs also slow the progression o left ventricular hypertrophy (in aortic regurgitation) and myocardial scar formation in expansion (eg, aneurysm formation after infarction).

c/d: ACEI/ARBs may lead to hyperkalemia, which in turn can cause conduction abnormalities. However, in the absence of this side effect, ACEI have no direct effect on heart conduction. They can be used safely in patients with atrioventricular block or polymorphic ventricular extrasystoles

f. angiotensin II is involved in atherogenesis. Hypertensive patients with iliofemoral atherosclerosis would therefore benefit form ACEI/ARBs that reduce the effects of angiotensin II.
This patient with intermittent nocturnal dyspnea, episodic cough and FH of atopy may have asthma despite his normal spirometry findings.

Asthma is an obstructive airway disease that occurs d/t hypersensitivity of the airways to various stimuli, including physical, chemical and allergenic irritants.

Personal or FH of other disease in allergic triad (allergic rhinitis, atopic dermatitis, allergic asthma) can aid in raising the suspicion for asthma. The diagnosis of asthma is typically confirmed by spirometry. Patients with asthma will demonstrate decreased FEV1 and peak expiratory flow rate on spirometry. These changes typically reversible with the use of a bronchodilator, usually an inhaled beta-adrenergic agonist such as albuterol.

When patient present with a history consistent with asthma but has normal spirometry values, bronchoprovocation techniques such as methacholine or histamine administration ,exercise or cold air inflation can considered to elicit asthma symptoms and confirm th diagnosis.

Methacholine is a msucarininc cholinergic agonist that causes bronchoconstriciton and increased airway secretions; a decrease in FEV1 after methacholine challenge indicates bronchial asthma.

a/e: ipratropium bromide and scopolamine are antagonist of muscarinic cholinergic receptors. Ipratropium is typically used in an inhaled form to treat bronchoconstriciton in patients with obstructive lung disease such as asthma or emphysema, and scopolamine is used for motion sickness

b. lavalbuterol is a beta-2 adrenergic agonist used in treatment of asthma and is sometimes sued in patients with adverse reactions to albuterol

d. phenoxybenzamine is a nonselective alpha-adrenergic antagonist used in treatment of pheochromocytoma.
Tay-Sachs is an AR neurodegenerative disorder commonly seen in the Ashkenazi Jews.

beta-hexoaminidase A def, resulting in accumulation of membrane glycolipid GM2 ganglioside within lysosome.

Patients are usually asymptomatic in the first few months, followed by progressive neurologic deterioration as glycolipids accumulate in the brain.

Clinical consequences:
-weakness, hypotonia, developmental regression, seizures, blindness and spasticity.
-macrocephaly and abnormal startle reflex
-cherry red macula where fovea is surrounded by white macula appearing as a halo. The halo is d/t ganglioside buildup in ganglion cells.

a. galactocerebroside builds up in Krabbe disease. Neurodegenration like Tay Sachs however, patients will also have peripheral neuropathy and optic atrophy.

b. globotriaosylceramide accumulates if Fabry. Angiokeratomas (benign cutaneous lesion of capillaries), peripheral neuropathy and glomerulopathy and typically present in adult hood.

c/g: cherry red macula is also found in Gaucher and Riemann-Pick. These guys however have hepatosplenomegaly
-beta-glucocerebroside accumulates in Gaucher
-Sphingomyelin accumulates in Neimenn-Pick

d. glycogen storage diseases include von Gierke disease and Pompe.
-von Gierke (glucose-6-phsphatase def) typically have hepatomegaly, hypoglycemia, seizures and/or lactic acidosis.
-Pompe disease (lysosomal alpha-1,4-glucosidase def) classically cause cardiomegaly and severe hypotonia.

f. mucopolysaccharidosis (eg, Hurler syndrome, Hunter syndrome) are lysosomal storage diseases that cause build up of GAGs such as heparin and derma tan sulfate. GAG accumulation causes nerucognitive decline as well as coarse facial features and skeletal abnormalities.
PAO2 (alveoli) = 104 mm Hg
pO2 generally reaches PAO2 by the time it passes through the first third of the alveolar capillaries d/t a high rate O2 diffusion through the respiratory membrane.

However, by the time oxygenated blood enters the systemic circulation, the pO2 drops to about 100 mm Hg d/t addition of deoxygenated blood from the bronchial circulation, intrapulmonary arteriovenous anastomoses, and Thebesian veins of the heart.

The discrepancy between alveolar and arterial O2 concentration is termed (A-a) gradient, which is normally between 5-15 mm Hg, with older individuals having a higher A-a d/t age related decrease in O2 diffusing capacity.

This patient has low PaO2 and PAO2 and a normal A-a gradient (71-60=11). This indicates that his low PaO2 is directly d/t his low PAO2 and not caused by V/Q mismatch or O2 diffusion impairment. Possible causes of hypoxemia in the setting of normal A-a gradient include
1. alveolar hypoventilation common in patients with suppressed central respiratory drive (eg, sedative, overdose, sleep apnea) or those with diseases that decrease inspiratory capacity (eg, myasthenia gravid, obesity).
2. inspiration of air at high altitude

a. diffusion impairment can be cause by thickening of the alveolar capillary membranes, such as alveolar hyaline membrane diseases. A-a gradient will increase because O2 in the alveoli cannot be transported into blood.

c. left to right shunt happens when the left heart (or systemic arterial circulation) is shunted into the right heart (or pulmonary artery). because blood in the left heart is oxygenated, left to right shunts doesn't lead to hypoxemia. This can occur with atrial or ventricular septal defects or patent ductus arterioles

d. right to left shunt occurs when venous blood bypasses the lung and enters the arterial circulation, thereby decreasing PaO2. The A-a gradient would increased. This type of hypoxemia occurs in patients with cyanotic congenital heart defects

e. V/Q mismatch is a common cause of hypoxemia. Poor ventilation of a lung segment with normal perfusion (eg, pneumonia, COPD) results in physiologic shunting, leading to increased A-a gradient.
This medication inhibits neprilysin, a metalloprotease that inactivates several peptide hormones, including bradykinin, glucagon, enkephalins and natriuretic peptides.

ANP is made by atrial cardiomyocytes in response to atrial stretch, which is indicative of systemic volume expansion.
-Lower blood pressure through peripheral vasodilation, natriuresis and diuresis.
-uses cGMP

Organs affected are:
1. kidney: dilates afferent arterioles = increase GFR and urinary excretion of Na and H20.
-it also limits Na reabsorption (in PCT and inner medullary of th recollecting duct)
-inhibits renin secretion
2. Adrenal gland: restrict aldosterone secretion, leading to an increase in Na and H2O excretion by kidneys
3. blood vessels: ANP relaxes vascular smooth muscle in arterioles and venues, producing vasodilation. It also increases capillary permeability, leading to fluid extravasation into the interstitium and a decrease in circulating blood volume.

b. duodenal mucosal cells produce many GI hormones such as gastrin, secretin and CCK. But none of them increases urinary output or decreases TPR

c. glomerular zone of the adrenal gland secretes aldosterone. Which would increase H2O and Na reabsorption causing the extracellular fluid to expand and BP to increase

d. oxytocin and ADH are 2 hormones produced by the posterior pituitary gland. Vasopressin increases water permeability of the renal collecting ducts, thereby increasing water reabsorption. Oxytocin stimulates uterine contractions in late pregnancy and facilitates breast milk ejection postpartum

e. JG cells secrete renin, which catalyzes the formation of angiotensin I from angiotensinogen. Angiotensin I is converted in the lungs into angiotensin II , which causes vastconstriction and aldosterone please.
Antiemetic drugs clinical uses:
1. motion sickness/hyperemesis gravid arum (promethazine)
a. antimuscarinics - scopolamine
b. antihistamines - diphenhydramine, meclizine, promethazine

2. Chemotherapy induced emesis
a. dopamine receptor antagonist - prochlorperazine, metoclopramide
b. 5-HT3 receptor antagonists - ondensetron and granisetron
c. neurokinin 1 (NK1) receptor antagonist: aprepitant, fosaprepitant

Vomiting reflex:
1. area postrema (4th ventricle) has chemoreceptor trigger zone that can respond to many neurotransmitters, drugs or toxins.
2. nucleus tracts solitaires (NTS) in medulla. Receives information from the area postrema, GI via the vagus nerve, vestibular system and CNS (eg, meninges, hypothalamus).

Neurons from the NTS project to other medullary nuclei and coordinate the vomitting process. The 5 major receptors involved in stimulating the vomiting reflex in the area postrema and adjacent vomiting center nuclei are M1, D2, H1, t-HT3, serotonergic and NK1.

5-HT3 receptor antagonists (eg, ondansetron, granisetron, dolasetron) are highly effective in preventing chemotherapy-inducedvomiting. 2 primary MOAs:
1. blocking vagus-mediated nausea and vomiting
2. blocking serotonin receptors in the area postrema and NTS

Other shit you can use is:
-NK1 receptor antagonists (eg, aprepitant), which inhibit substance P and help prevent both acute vomitinga nd delayed emesis
-Dopamine receptor antagonists (eg, metoclopramide), associated with drowsiness and dystonic reactions

a/d: histamine blockers and antimuscarinic/anticholinergic agents are most helpful for vestibular nausea and vomiting.

b. motion regulates inter digestive migrating contractions. Erythromycin is a motion receptor agonist used for gastroparesis

c. Mu opioid receptor agonists (eg, morphine) are useful for cancer related pain control but often have side effects such as nausea and vomiting.
Primary hyperPTH classic symptoms:
-bone pain
-renal stones
-GI disturbances (eg, peptic ulcer disease)
-psychiatric disorders

"bones, stones, abdominal groans and psychic moans."

asymptomatic hypercalcemia is the most common presentation nowadays d/t routine measurement of calcium in the chemistry profile.

1. PTH increases renal tubular Calcium reabsorption (although most patients have hypercalciuria).
2. increased production of calcitriol (1,25 dihydroxyvitamin D) in the kidneys causing increased GI calcium absorption.
3. PTH mediated increase in bone resorption (via osteoclast activation)

-Hypophosphatemia as PHP decreases phosphate resorption in the proximal renal tubules.

Morphology, skeletal finding
-involves cortical (compact) bone in the appendicular skeleton ( the pectoral girdle, pelvic girdle and limbs).
-subperiosteal erosions in phalanges of the hand, a granular "salt and pepper" skull, and osteolytic cystic the long bones

a disorganized lamellar bone structure in a mosaic pattern = Paget disease. Serum calcium and phosphorous are normal.

b. osteoid matrix accumulation around traveculae is seen in osteomalacia. Hits shows excessive unmineralized osteoid with widened osteoid seams. patients will typically have low urinary calcium.

c. persistence of the primary spongiosa in the medullary cavity with no mature trabeculae is a classic fining of osteoporosis (i.e., "marble bone disease"). Osteoporosis is caused by decreased osteoclastic bone resorption, which results in accumulation of woven bone and diffuse skeletal thickening

e. trabecular thinning with fear interconnections is characteristics of osteoporosis. Although longstanding PHP causes thinning of cortical bone, the trabecular architecture remains relatively preserved.