Block 10

Question 1

Metoformin : mechanism

Answer 1

• inhibits mitochondrial glycerophosphate dehydrogenease and complex I—> decrease in cellular energy stores causes AMPK activation –> decreased hepatic gluconeogenesis.
• increase peripheral glucose utilization. It doesnt increase insulin endogenous secretion and doesnt cause hypoglycemia when used as monotherapy.

Question 2

46, XX, del(22)q(11) leads to

Answer 2

Di george syndrome

• hypertelorism
• micrognathia
• cleft palate
• cardiac defects (teratology of fallot, interuptted aortic arch)

Question 3

Fibrillin -1

Answer 3

Major component of microfibrils that form a sheath around elastin fibers

• fibrillin acts as a scaffold for deposition of elastin extruded from connective tissue cells.
• defects in fibrillin cause mechanical weakining in the connective tissues and abnormal activation of TGF-beta –> marfan syndrome

Question 4

Craniopharyngyomas

Answer 4

• arises from remnants of rathkes pouch
• they have 3 components : solid(actual tumor cells ), cystic (filled with machinery oil liquid) and calcified component.
• symptoms include headache, visual field defects and hypopituratism, –> growth retardation in children

Question 5

Foscarnet mechanism

Answer 5

Pyrophosphate analog that doesnt require intracellular activation.
-directly inhibits both DNA polymerase in Herpesvirus and RT in HIV.

Question 6

Diabetes insipidus , features

Answer 6

• polyuria, polydipsia.
• due to impaired ADH activity –> large volumes of dilute urine
• if DI is central the most probable cause is injury or trauma to hypothalamic nuclei (not posterior pituitary)
• injection of exogenous ADH can distinguish between central and nephrogenic.

Question 7

Bronchial arteries

Answer 7

Carries blood to the bronchi and bronchioles and together with the pulmonary artery, form dual supply to the lungs.

• the bronchial veins returns only a portion of this blood to the right heart via azygos vein and hemiazygos veins
• most of the blood supplied by bronchial arteries return to the heart via the pulmonary veins.
• this reuslt in a mixing of deoxygenated blood with oxygenated blood (PaO2 =104 mm Hg —-> after mixing —> PaO2= 100 mmHg)

Question 8

B6 deficincy

Answer 8

Cheiliosis , glossitis, dermatitis, siderblastic anemia and affective symptoms

Question 9

Fenestrae

Answer 9

Small pores within endothelial cells that allow free fluid exchange between intra and extravascular spaces.

Question 10

Small intestinal bacterial overgrowth

Answer 10

Charactrized by overproduction of VIT K and folate, associated with nause, bloating, abdominal discomfort and malabsorption.
- this can arise after gastric bypass surgery with roux en y–> closed ended gastrodudenal limb in which bacteria can proliferate in

Question 11

CYTARABINE

Answer 11

Pyrimidine analogue . Inhibit DNA Polymerase –> used to treat leukemia (AML) and Lymphomas

Question 12

Needle shaped, negatively birefringent crystals

Answer 12

Monosodium urate crystals, seen under polarized light microscopy and may be present both intra and extracellular.
- they are seen in GOUT patients, usually at joints

Question 13

T.gondii in HIV patients

Answer 13

HIV patients infected with T.gondii can develop encephalitis with multiple necrotizing brain lesions.

• resulting in :fever, headache, altered mental status, and focal neurological findings.
• in HIV patients with seizures, multiple ring enhancing lesion with mass effect, cerebral toxoplasmosis is a likely diagnosis.
• treatment include : pyrimethamine, and sulfadiazine along with leucovorin.

Question 14

Medial geniculate bodies are part of

Answer 14

Auditory pathway, as well as inferior colliculi

Question 15

Diarrhea DD(VIPOMA vs inflammatory vs osmotic)

Answer 15

Vipoma= doesn’t improve with dietary modification (in contrast to osmotic such as lactose intolerance), and doesnt have blood or pus ( while inflammatory diarrhea have pus and blood )

Question 16

Paroxysmal nocturnal hemoglobinuria

Answer 16

• increased complement mediated intravascular RBC lysis due to impaired synthesis of GPI anchor for decay accelerating factor that protects RBC membrane from complement.
• acquired mutations in a hematopoietic stem cell. (Increase incidence of leukemia)
  -pink or red urine
  -triad of coombs negative hemolytic anemia, vein thrombosis and pancytopenia
• CD55/59 negative RBC on flow cytometry
  Treatment is eculizumab (inhibit MAC formation)

Question 17

Hodgkin lymphoma clinical findings

Answer 17

• non tender lymphadenopathy
• reed stenberg cells
• B symptoms ( fever, night sweats and weight loss)
• Bimodal age distribution - peaks in the 20s and 60s.

Question 18

Pathologic findings in the adrenal galnd in patient with cushing disease and syndrome

Answer 18

1. Cushing syndrome : (adrenal adenoma or carcinoma): benign tumors consists of cells similar to zona fasciculata, malignant tumor can exhibit considerable pleomorphism. Along with atrophy of zona fasciculata and reticularis in the uninvolved cortex regions.
2. Cushing disease/ectopic ACTH: billateral adrenocortical hyperplasia involving the zona fasciculata and zona reticularis that can be diffuse or nodular.

Question 19

Prenatal Hep B infection

Answer 19

Risk factors: 
- maternal viral load
-maternal HBeAg positive
Clinical findings: 
-infant usually immunutolerant (normal or mildely elevated liver enzymes) 
-high risk for chronic infection
- high viral load and HBeAg positive
Prevention : 
-maternal Antiviral therapy in some cases
-newborn hepatitis B vaccination and immunuglobulin within 12 hrs
-routine immunization 
-serology 3 month after the 3rd dose

Question 20

Degree of 21 hydroxylase deficiency;

Answer 20

1. Non-classic, delayed : mild , premature pubarche or sexual precocity in school age children , young women with acne, hirsutism and menustral irregularity.
2. Classic non salt wasting/ moderate: girls present at birth with ambiguous genetalia, boys present at 2-4 years with signs of early virilization
3. Severe: classic salt wasting: girls present at birth with ambigious genetalia
   Boys present at 1-2 weeks with failure to thrive, dehydration, hyperkalemia and hyponatremia

Question 21

Von willebrand disease : parameters , assay

Answer 21

Ristoectin cofactor assay shows no platelet aggregation.
-treatment : desmopressin –> increase secretion from endothelial cells.
Pc= normal
BT= increased
PT= normal
PTT= increased

Question 22

Niacin deficiency

Answer 22

Dermatitis
Dementia
Diarrhea

Question 23

Platelets syndromes

1. Bernard soulier
2. Glanzmann thrombasthenia
3. Immune thrombocytopenia
4. TTP

Answer 23

1. Bernard oulier = defect in GpIb (decreased ) defect in plaetlet to vWF adhesion
2. Glanzmann: defect in integrin aIIb ß3 (GpIIa/IIIa) –> defect in platelet to platelet aggregation. (Decreased BT and normal PC)
3. ITP= anti GpIIa/IIIb antibodies -> splenic macrophages consumption of antibody antigen complex –> (decreased PC and increased BT). Treatment is steroids, IVIG, splenectomy
4. TTP: inhibition of adamts13 (vWF metalloprotease) –> decreased degredation of vWF multimers –> large vWF multimers –> increased platelet adhesion and aggregation –>thrombosis. (Decreased PC and increased BT). Shistocytes present, increased LDH. Tx: plasmapheresis.

Question 24

Leukocyte adhesion deficiency

Answer 24

• recurrent skin and mucosal bacterial infections (omphalitis, periodonitis (no pus - lack of neutrophils at inflammation sites, poor wound healing)
• delayed umbilical cord seperation
• marker peripheral leukocytosis with neutrophillia.
• CD 18 absence( necessary for formation of integrin)

Question 25

Congenital torticollis

Answer 25

Develops by 2-4 weeks of age, most commonly caused by virth trauma (breech delivery ..) or malposition of the head in utero (fetal macrosomia or oligohydroamnios), both of which can result in SCM injury and fibrosis. - rarely it can be due to cervical spine deformities. - children have usually additional musculoskeletal anomalies, including hip dysplasia, metatarsus adductus. - diagnosis made clinically. - conservative therapy and stretching exercises.

Question 26

Wiskott aldrich syndrome

Answer 26

- X-linked ,-defect in cytoskeletion rearrangment - thrombocytopenia, - immunodeficiency and - eczemma

Question 27

Hydroxyurea in HbS

Answer 27

Increase HbF

Question 28

Mu opoid analgesics effect on smooth muscles

Answer 28

- it can cause contraction of sphincter of oddi, leading to spasm and increase in common bile duct pressure(its affects is contraction of smooth muscle cells)

Question 29

Korsakoff syndrome (permanent changes)

Answer 29

-associated with damage to the anterior and dorsomedial thalamic nuclei --> memory loss and confabulation --> anterograde amnesia - the impairment in memory and learning is usually permanent in these patients even if treated with thiamine. (Symptoms of thiamine deficiency are ataxia, oculomotor dysfunction, and confusion, memory loss and confabulation)

Question 30

Thiamine deficiency

Answer 30

1. Beriberi : adult beriberi categorized as dry or wet depending on cardiac involvement. - Dry beriberi is characterized by symmetrical peripheral neuropathy of distal extremities , with resulting sensory and motor impairments. - Wet beriberi: include the addition of cardiac involvement(cardiomypathy, high output congestive HF, peripheral edema, and tachycardia). 2. Wernicke korsakoff syndrome

Question 31

Leukotrines

Answer 31

- under the infleuance of inflammatory stimuli, cell membrane phopholipids release arachidonic acid, a precursor to the eicosanoid inflammatory mediatiors. - the most potent chemotatctic eicosanoid is leukotrine B4. - the cysteinyl containing leukotriens (LTC4,LTD4,LTE4) causes bronchospasm and increase bronchial mucus secretion and are important in asthma pathogenesis.

Question 32

Down syndrome dysmorphic features

Answer 32

1. Epicanthal fold 2. Upslanting papebral fissure 3. Protruding tongue 4. Excessive skin at the nape of the neck 5. Birth weight and height below average 6. Cardiac defects are present in >50% of cases 7. Hypotonia and weak startle (moro) reflex

Question 33

Dubin johnson syndrome

Answer 33

Benign AR, defective hepatic excertion of billirubin glucuronides --> mutation in canlicular membrane trasport protein. - individulas can develop episodes of jaundice which may only become evident in the context of trigger. - liver appears black due to impaired excertion of epinephrine metabolites that accumulates within lysosomes . - rotor syndrome as a milder disease.

Question 34

Primary central nervous sytstem lymphoma

Answer 34

- PCNSL, diffuse, large cell - non hodgkin lymphoma , of B-cell origin, usually occurs as a late complication of HIV. - EBV is identified in almost all cases, for diagnosis , EBV-PCR and brain biopsy. - -its the second most common cause of ring enhancing lesion with mass effect in HIV (after T.gondii) - classically large solitary lesions are more likely to suggest PCNSL rather than toxoplasmosis, however multiple lesions are also seen

Question 35

Ristocetin assay

Answer 35

Activates vWF to bind GpIb.failure of aggregation occurs in vW disease and bernard soulier syndrome

Question 36

VIPOMA - clinical

Answer 36

Excess VIP secretion due to pancreatic islet tumor.(WDHA syndrome -clinical signs synonym) 1. Watery diarrhea 2. Hypokalemia 3. Achlorhydria

Question 37

Oral antidiabetics:

Answer 37

1. Insulin secretagogues : sulfonylureas and meglitinides --> secretion of insulin by inhibiting ßcell K-ATP channels. 2. Biguanides: metformin --> stimulate AMPK, decrease glucose production and insulin resistance 3. Thiazollidinediones: (pioglitazone, rosiglitazone) --> activates transcription regulator PPAR-¥, decreasing insulin resistance 4. GLP-1 agonist: (exenatide): increase glucose dependent insulin secretion, decrease glucagon secretion , and delays gastric emptying. 5. DPP4 inhibtors: (sitagliptin, saxagliptin) : increase endogenous GLP-1 and GIP levels 6. å-glucosidae inhibitors: (acarbose, miglitol) -> decrease disaccharide absorbion (intestinal) 7. SGLT2- inhibtors: (canagliflozin, dapagliflozin ) -> increase renal glucose excretion.

Question 38

Cisplastin side effect

Answer 38

Nephrotoxicity -- prevented with amifostine (free radical scavenger) and chloride ( saline) diuresis.

Question 39

Aplastic anemia

Answer 39

Bone marrow failure due to hematopoieitic stem cell deficiency (CD34). Caused by autoimmune , infections (B19, EBV), drugs (chloramphenicol, carbamazepine and sulfonamides) , exposure to radiation or toxins. Clinical findings: pancytopenia Diagnosis: biopsy showing hypocellular bone marrow composed of mainly fat and stromal cells.

Question 40

The right lateral geniculate body recieves from | Left lateral geniculate body

Answer 40

1. Right lateral geniculate body : receives visual information from the tight temporal hemiretina and left nasal hemiretina 2. Left lateral geniculate body receives visual information from left temporal hemiretina and right nasal hemiretina.

Question 41

Gout arthritis

Answer 41

Present with acute onset of severe joint pain, warmth, erythema, and swelling - diagnosis is done by synovial fluid analysis, which shows increased WBC. - gout occurs most commonly in joints where cooler temperatures favors crystal formation, especially in distal lower extremity (first metatarsophalangeal joint, ankle, knee). - uotake of urate crystals --> free radical release --> cytokines production --> joint inflammation.

Question 42

Normal alveolar pO2

Answer 42

Is 104 mm Hg, which lies between the tracheal 150 mm Hg and venous 40 mm Hg. Increase in the alveolar pressure means there is V/Q mismatch in which perfusion isnt adequate ( O2 stays in the alveoli and doesnt leave to the blood ). this can be a result of PE

Question 43

Cyclophosphamide side effect

Answer 43

Hemorrhagic cystitis, can be prevented by mesna (thiol group of mesna binds toxic metabolite) or N-Actylcysteine

Question 44

rasburicase

Answer 44

Catalyzes metabolism of uric acid to allantoin. Prevention and treatment of tumor lysis syndrome

Question 45

Germ tube is diagnostic for

Answer 45

Candida. Albicans (see pic)

Question 46

Congeintal hypothyrodism

Answer 46

-initially normal at birth - symptoms : after maternal T4 wanes - lathargy -large fontanelle -protrouding tongue -umbilical hernia -poor feeding -constipation - dry skin -jaundice Diagnosis: increased TSH and decreased free T4 levels Newborn screening TX: levothyroxine

Question 47

Valproate

Answer 47

- anticonvulsant and mood stabillizer - blocks voltage gated Na+ and enhances GABA synthesis and release . - valproate effectively treats absence, myoclonic and generalized tonic clonic seziures. - its the drug of choice for myoclonic seziures

Question 48

VIP function

Answer 48

It stimulates pancreatic HCO3-, and Cl- secretion, > bind to intestinal epithelial cells ---> cAMP increased -->Na+, Cl-, H2o secretion into the bowel.

Question 49

Treatment for 21 hydroxylase deficiency

Answer 49

Corticosterois --> inhibits ACTH

Question 50

Metformin contraindication

Answer 50

-Renal dysfunction - CHF -alcoholism (The reason is due --> metformin --> increase intestinal lactate production by inhibiting mitochondrial enzymes, --> also it reduces hepatic metabolism of lactate(due to decreased gluconeogenesis) --> lactic acidosis. - the disease above are at high risk to develop lactic acidosis even without metformin

Question 51

Hepatic encephalopathy

Answer 51

- increased circulatory levels of ammonia and other neurotoxins due to failure of the liver to metabolize waste products. - under normal conditions, astrocytes regulate neurotansmission by taking up glutamate present in synapse to prevent excessive neuronal excitation. Through the action of glutamine synthase --> glutatmate and ammonia --> glutamine - glutamine is then released by astrocytes --> taken up by neurons and converted to glutamate and used as neurotransmitter. - excess ammonia--> increased glutamine production --> astrocytes swelling and impaired glutamine release ---> decrease glutamate in neurons --> disruption of excitatory neurotransmission

Question 52

Pleuritic chest pain

Answer 52

Sharp ,localized , often severe pain that is exacerbated by coughing, breathing or changing position. -the phrenic nerve carries pain fibers from the diaphragmatic and mediastinal pleura--> irritation causes sharp pain --> irradiation of C3-C5 distribution at the base of the neck and over the shoulder.

Question 53

Causes of gout

Answer 53

1. Increased urate production : - myelo/lympho -proliferative disorder - tumor lysis syndrome - HGPT deficiency 2. Decreased clearance - CKD - thiazide /loop diuretics

Question 54

Chest tube drianage in the 4th and 5th intercostal space can traverse which muscle

Answer 54

Serratus anterior.

Question 55

Factor V leiden

Answer 55

Production of mutant factor V (Arg506GIn mutation near cleavage site). That is resistant to degredation by protein C. - leads to DVT, cerberal vein thrombosis, recurrent pregnancy loss

Question 56

Infantile beriberi

Answer 56

-due to thiamine deficiency - age 2-3 months with fulminant cardiac syndrome -cardiomegaly Tachycardia, cyanosis, dyspnea and vomiting.

Question 57

Motillin

Answer 57

Produced by dudenal mucosa and stimulates smooth muscle contraction in the upper GI tract. - erythromycin act as agonist at mitillin receptor --> side effects

Question 58

Superior vena cava syndrome

Answer 58

Dyspnea, cough and swelling of the face, neck and upper extremities - headache ,dizziness, and confusion may occur due to cerebral edema. - elevated intracranial pressure-- dilated collateral vein may be seen in the upper toros.

Question 59

Eculizumab

Answer 59

Inhibit MAC formation in complement | Used for paroxysmal nocturnal hemoglobinuria

Question 60

Robertsonian translocation

Answer 60

- translocation down syndrome can be inherited from an unaffected parent with balanced translocation. - it occurs between 2 acrocentric, nonhomologous chromosomes (eg 14,21) --> the result is fusion of 2 long arms. - the carriers usually can leads to monomy 14, monosomy 21, and trisomy 14 these are incompatible with life thus --> multiple abortions .