Block 10 Flashcards
Metoformin : mechanism
- 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.
46, XX, del(22)q(11) leads to
Di george syndrome
- hypertelorism
- micrognathia
- cleft palate
- cardiac defects (teratology of fallot, interuptted aortic arch)
Fibrillin -1
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
Craniopharyngyomas
- 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
Foscarnet mechanism
Pyrophosphate analog that doesnt require intracellular activation.
-directly inhibits both DNA polymerase in Herpesvirus and RT in HIV.
Diabetes insipidus , features
- 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.
Bronchial arteries
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)
B6 deficincy
Cheiliosis , glossitis, dermatitis, siderblastic anemia and affective symptoms
Fenestrae
Small pores within endothelial cells that allow free fluid exchange between intra and extravascular spaces.
Small intestinal bacterial overgrowth
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
CYTARABINE
Pyrimidine analogue . Inhibit DNA Polymerase –> used to treat leukemia (AML) and Lymphomas
Needle shaped, negatively birefringent crystals
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
T.gondii in HIV patients
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.
Medial geniculate bodies are part of
Auditory pathway, as well as inferior colliculi
Diarrhea DD(VIPOMA vs inflammatory vs osmotic)
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 )
Paroxysmal nocturnal hemoglobinuria
- 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)
Hodgkin lymphoma clinical findings
- non tender lymphadenopathy
- reed stenberg cells
- B symptoms ( fever, night sweats and weight loss)
- Bimodal age distribution - peaks in the 20s and 60s.
Pathologic findings in the adrenal galnd in patient with cushing disease and syndrome
- 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.
- Cushing disease/ectopic ACTH: billateral adrenocortical hyperplasia involving the zona fasciculata and zona reticularis that can be diffuse or nodular.
Prenatal Hep B infection
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
Degree of 21 hydroxylase deficiency;
- Non-classic, delayed : mild , premature pubarche or sexual precocity in school age children , young women with acne, hirsutism and menustral irregularity.
- Classic non salt wasting/ moderate: girls present at birth with ambiguous genetalia, boys present at 2-4 years with signs of early virilization
- 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
Von willebrand disease : parameters , assay
Ristoectin cofactor assay shows no platelet aggregation.
-treatment : desmopressin –> increase secretion from endothelial cells.
Pc= normal
BT= increased
PT= normal
PTT= increased
Niacin deficiency
Dermatitis
Dementia
Diarrhea
Platelets syndromes
- Bernard soulier
- Glanzmann thrombasthenia
- Immune thrombocytopenia
- TTP
- Bernard oulier = defect in GpIb (decreased ) defect in plaetlet to vWF adhesion
- Glanzmann: defect in integrin aIIb ß3 (GpIIa/IIIa) –> defect in platelet to platelet aggregation. (Decreased BT and normal PC)
- ITP= anti GpIIa/IIIb antibodies -> splenic macrophages consumption of antibody antigen complex –> (decreased PC and increased BT). Treatment is steroids, IVIG, splenectomy
- 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.
Leukocyte adhesion deficiency
- 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)
Congenital torticollis
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.
Wiskott aldrich syndrome
- X-linked ,-defect in cytoskeletion rearrangment
- thrombocytopenia,
- immunodeficiency and
- eczemma
Hydroxyurea in HbS
Increase HbF
Mu opoid analgesics effect on smooth muscles
- 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)
Korsakoff syndrome (permanent changes)
-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)
Thiamine deficiency
- 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). - Wernicke korsakoff syndrome
Leukotrines
- 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.
Down syndrome dysmorphic features
- Epicanthal fold
- Upslanting papebral fissure
- Protruding tongue
- Excessive skin at the nape of the neck
- Birth weight and height below average
- Cardiac defects are present in >50% of cases
- Hypotonia and weak startle (moro) reflex
Dubin johnson syndrome
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.
Primary central nervous sytstem lymphoma
- 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
Ristocetin assay
Activates vWF to bind GpIb.failure of aggregation occurs in vW disease and bernard soulier syndrome
VIPOMA - clinical
Excess VIP secretion due to pancreatic islet tumor.(WDHA syndrome -clinical signs synonym)
- Watery diarrhea
- Hypokalemia
- Achlorhydria
Oral antidiabetics:
- Insulin secretagogues : sulfonylureas and meglitinides –> secretion of insulin by inhibiting ßcell K-ATP channels.
- Biguanides: metformin –> stimulate AMPK, decrease glucose production and insulin resistance
- Thiazollidinediones: (pioglitazone, rosiglitazone) –> activates transcription regulator PPAR-¥, decreasing insulin resistance
- GLP-1 agonist: (exenatide): increase glucose dependent insulin secretion, decrease glucagon secretion , and delays gastric emptying.
- DPP4 inhibtors: (sitagliptin, saxagliptin) : increase endogenous GLP-1 and GIP levels
- å-glucosidae inhibitors: (acarbose, miglitol) -> decrease disaccharide absorbion (intestinal)
- SGLT2- inhibtors: (canagliflozin, dapagliflozin ) -> increase renal glucose excretion.
Cisplastin side effect
Nephrotoxicity – prevented with amifostine (free radical scavenger) and chloride ( saline) diuresis.
Aplastic anemia
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.
The right lateral geniculate body recieves from
Left lateral geniculate body
- Right lateral geniculate body : receives visual information from the tight temporal hemiretina and left nasal hemiretina
- Left lateral geniculate body receives visual information from left temporal hemiretina and right nasal hemiretina.
Gout arthritis
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.
Normal alveolar pO2
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
Cyclophosphamide side effect
Hemorrhagic cystitis, can be prevented by mesna (thiol group of mesna binds toxic metabolite) or N-Actylcysteine
rasburicase
Catalyzes metabolism of uric acid to allantoin. Prevention and treatment of tumor lysis syndrome
Germ tube is diagnostic for
Candida. Albicans (see pic)
Congeintal hypothyrodism
-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
Valproate
- 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
VIP function
It stimulates pancreatic HCO3-, and Cl- secretion, > bind to intestinal epithelial cells —> cAMP increased –>Na+, Cl-, H2o secretion into the bowel.
Treatment for 21 hydroxylase deficiency
Corticosterois –> inhibits ACTH
Metformin contraindication
-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
Hepatic encephalopathy
- 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
Pleuritic chest pain
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.
Causes of gout
- Increased urate production :
- myelo/lympho -proliferative disorder
- tumor lysis syndrome
- HGPT deficiency - Decreased clearance
- CKD
- thiazide /loop diuretics
Chest tube drianage in the 4th and 5th intercostal space can traverse which muscle
Serratus anterior.
Factor V leiden
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
Infantile beriberi
-due to thiamine deficiency
- age 2-3 months with fulminant cardiac syndrome
-cardiomegaly
Tachycardia, cyanosis, dyspnea and vomiting.
Motillin
Produced by dudenal mucosa and stimulates smooth muscle contraction in the upper GI tract.
- erythromycin act as agonist at mitillin receptor –> side effects
Superior vena cava syndrome
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.
Eculizumab
Inhibit MAC formation in complement
Used for paroxysmal nocturnal hemoglobinuria
Robertsonian translocation
- 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 .
