Pathoma Flashcards
Genetic disease associated with Apo-E allele mutation
Late set Alzhemiers
Disease caused by Amyloid precursor protein, presenilin 1 gene on chromosome 14, presenilin 2 gene on chromosome 1
Early onset Alzheimers
There is a killed (Salk) and live (Sabin) vaccine against the polio virus. Which one is better at prolonged synthesis and secretion of local mucosal IgA?
Live virus
What kind of test is used to compare the means of 2 groups of subjects?
Two-sample T-test
What does acetylcholinesterase in the amniotic fluid typically indicate?
Failed fusion (Neural tube defect) Note: Alpha-fetoprotein (AFP) in the amniotic fluid suggests the same thing. Lack of close of the neural tube allows for these things to leak out into the amniotic fluid.
TLR found on macrophages that recognizes the PAMP (lipopolysaccharide) on the outer membrane of gram negative bacteria.
CD-14
TLR activation results in upregulation of ______, a nuclear transcription factor that activates immune response genes leading to production of multiple immune mediators.
NF-kappaB
Enzyme that causes arachidonic acid release from the phospholipid cell membrane.
Phospholipase A2.
Remember, AA precursor of prostaglandins and thromboxanes (via cyclooxygenase COX) or leukotrienes (via 5-lipooxygenase).
What function do the prostaglandins PGI2, PGD2, and PGE2 have?
They all three mediate vasodilation and increased vascular permeability.
Note: PGE2 also causes fEver and pain.
What type of immune cells will you find toll-like receptors?
innate immune cells (macrophages and dendritic cells).
What type of leukotriene will attract and activate neutrophils?
LTB4
Note: C5a (complement), IL-8 and bacterial products also attract and activate neutrophils.
Which type of leukotrienes will contraction of smooth muscle (vasoconstriction and bronchospasm), as well as increased vascular permeability?
LTC4, LTD4, and LTE.
What type of cell is activated by one of these three methods:
- Tissue trauma
- Complement proteins C3a and C5a
- Cross linking the cell surface IgE by antigen
Mast cells-which are widely distributed throughout connective tissue.
Note: when they are activated, they release preformed histamine granules, which mediate vasodilation of the arterioles and increased vascular permeability.
Three ways to activate complement are:
Classical pathway
Alternative pathway
Mannose-binding lectin pathway
What is each ones of these about?
- Classical: C1 binds IgG or IgM that is bound to antigen.
* ***Mneumonic: GM makes classic cars. - Alternative: microbial products directly activate complement.
- MBL: MBL binds to mannose on microorganisms, which activates complement.
All complement pathways result in production of C3 convertase (mediates C3–>C3a and C3b), which in turn produces C5 convertase (mediates C5–>C5a and C5b). C5b complexes with C6-C9 to form the membrane attack complex (MAC).
What do the following cause to happen:
- C3a and C5a
- C5a
- C3b
- Mac
- C3a & C5a: anaphylatoxins: trigger mast cell degranulation, resulting in histamine-mediated vasodilation and increased vascular permeability.
- C5a: Chemotaxis for neutrophils
- C3b: Opsonin for phagocytes
- MAC: Lyses microbes by creating a hole in the cell membrane.
Inactive proinflammatory protein produced in the liver which is activated upon exposure to subendothelial or tissue collagen, which in turn activates:
- Coagulation of fibrinolytic systems
- Complement
- Kinin System—>cleaves kininogen to bradykin, which mediates vasodilation and increased vascular permeability (similar to histamine), as well as pain
Hageman Factor (Factor XII)
What are the five cardinal signs of inflammation?
- Redness (rubor)
- Warmth (calor)
- Swelling (tumor)
- Pain (dolar)
- Fever
In inflammation, rubor and calor (redness and warmth) are due to vasodilation, which results in increased blood flow. What are the key mediators of this?
Histamine, Prostaglandins (PGI2, PGD3, and PGE2), and bradykinin.
Inflammation during swelling occurs due to leakage of fluid from POSTCAPILLARY venues into the interstitial space (exudate). What are are the key mediators?
- Leukotrienes: cause endothelial cell contraction.
2. Tissue damage: results in endothelial cell disruption
You will see pain (dolar) involved with inflammation. What mediates this pain?
Bradykinin and PGE2 sensitize sensory nerve endings.
Macrophages are responsible for fever during inflammation. This occurs when pyrogens (LPS from bacteria) cause macrophages to release ________ and _________, which increase COX activity in per vascular cells of the hypothalamus, resulting in PGE2, which raises the temp set point.
IL-1 and TNF
In acute inflammation, you will neutrophils will:
- Marginate (due to vasodilation)
- Roll
- Adhere
- Transmigrate and chemotax
- Phagocytose
What causes the rolling?
P-selectin (released from Weibel-Palade bodies–>from histamine)
E-sectin (induced by TNF and IL-1)
Remember TNF and IL-1 are released from macrophages and also cause fever.
In acute inflammation, you will neutrophils will:
- Marginate (due to vasodilation)
- Roll
- Adhere
- Transmigrate and chemotax
- Phagocytose
- What are the molecules that cause cellular adhesion?
- What molecules cause the upregulation of these adhesion molecules?
- ICAM and VCAM: on endothelium upregulated by TNF and IL-1.
- Integrin: on leukocytes upregulated by C5a and LTB
Interaction between the CAMs and Integrins result in firm adhesion of leukocytes to the vessel wall.
Autosomal recessive defect of integrins (CD18 subunit)
**Clinical features include delayed separation of umbilical cord, increased circulating neutrophils, and recurrent bacterial infections that lack pus formation.
LAD: Leukocyte adhesion deficiency
In acute inflammation, you will neutrophils will:
- Marginate (due to vasodilation)
- Roll
- Adhere
- Transmigrate and chemotax
- Phagocytose
What two opsonins are important in phagocytosis of pathogens or necrotic tissue?
IgG
C3b
Autosomal recessive protein trafficking defect (caused by microtubule defect) characterized by impaired PHAGOLYSOSOME FORMATION.
Characterized by:
-Increased risk of pyrogenic infection-
Neutropenia (due to intramedullary death of neutrophils)
-Giant granules in leukocytes (due to fusion of granules arising from the Golgi)
-Defective primary hemostasis (due to abnormal dense granules platelets).
-Albinism (pigment can’t move into keratinocytes).
-Peripheral neuropathy (can’t traffic protein from nerve to nerve ending distally).
Chediak-Higashi syndrome
What is the most effective method of phagocytosis?
O2-dependent killing.
(HOCL- generated by oxidative burst in phagolysosomes destroys phagocytosed microbes.
Name that enzyme:
- O2 —->O2-
- O2—->H2O2
- H2O2—->HOCL- (bleach): found in lysosomes in neutrophiles
- NADPH oxidase (oxidative burst)
- superoxide dismutase (SOD)
- Myeloperoxidase (MPO)
- Disease caused by NADPH oxidase defect (so no O2—>O2—->H2O2—>HOCl-). It is either X-linked or autosomal recessive). Leads to recurrent infection and granuloma formation with catalase-positive organisms.
- Two catalase-+ organisms that are typically recurrent in this diease.
- Chronic granulomatous disease (CGD)
2. S. aureus, PSEUDOMONAS CEPACIA.
Chronic granulomatous disease (CGD) is characterized by poor O2 dependent killing and is typically due to NADPH oxidase defect. What test is used to screen for CGD?
Nitroblue tetrazolium test-
Leukocytes are incubated with NBT dye, which turns blue if NADPH oxidase can convert O2 to O2- but remains colorless if NADPH oxidase is defective.
What is the difference between chronic granulomatous disease and MPO deficiency?
Chronic granulomatous disease: NADPH oxidase deficiency-positive NBT (nitroblue terazoium test…will be clear results). No O2 to O2-.
Myeloperoxidase deficiency: defective conversion of H2O2 to HOCl- INCREASED RISK OF CANDIDA INFXN.–>NBT test will turn blue (b/c NAPDH oxidase is fine).
What happens to neutrophils after resolution of infection?
Apoptosis within 24 hours after resolution of inflammatory stimulus.
In acute inflammation, neutrophils will be on the scene first. But macrophages predominate after neutrophils and peak 2-3 days after inflammation begins. They arrive in the tissue the same way neutrophils do.
After macrophages ingest organisms via phagocytosis, how do they kill them?
O2 INDEPENDENT killing: use enzymes in secondary granules (such as lysozyme).
Macrophages manage the next next of inflammatory process (after neutrophils). They can facilitate:
- Resolution and healing.
- Continued acute inflammation (IL-8 recruits more neutrophils)
- Abscess (macrophages mediate fibrogenic growth factors and cytokines)
- Chronic inflammation: macrophages present antigen to activate CD4+ helper T cells, which secrete cytokines that promote chronic inflammation.
What are the anti-inflammatory cytokines that cause resolution and healing after an acute inflammation?
- IL-10 and TGF-beta
Progenitor T-cells are formed in the bone marrow, but are further developed in the thymus where the T-cell receptor (TCR) undergoes rearrangment and becomes CD4+ helper T-cells or CD8+ cytotoxic T cells.
Which MHC do CD4+ t-cells recognize?
Which MHC do CD8+ t-cells recognize?
- CD4+ (Helper T’s): MHC II
- CD8+ (Cytotoxic T’s): MHC I
Remember MHC II is antigen from outside of the cell (bacteria, for example.
MHC I is antigen from inside of the cell (either self antigen or viral antigen).
Activation of T-cells require two steps:
- Activation of antigen/MHC complex.
2 Additional signal. - In the case of CD4+ T-cells, they will bind MHC II. What is the second step in activation?
- In the case of CD8+ T-cells, they will bind MHC I. What is the second step in activation?
- B7 (antigen presenting cells)—>binds CD28 (on CD4+ helper T’s).
- IL-2 from CD4+ helper T’s is the second step in activation of CD8+ cells.
CD4+ T-Helpers can be divided into two categories:
TH1
TH2
What do each of these types of cells “help”?
TH1: stimulates CD8+ T-cells (via T-cell growth factor) and macrophages (via IFN-gamma.)
TH2: stimulates B-cell class switching to IgG and IgE via IL-4, eosinophil chemotaxis and activation, as well as maturation of B cells to plasma cells and class switching to IgA via IL-5, as well as secrete IL-10 (which inhibits TH1 phenotype).
How do cytotoxic T-cells kill? (2 ways)
- Secretion of perforin and granzyme; perforin creates pores that allow granzyme to enter the target cell, activating apoptosis.
- Expression of FasL, which bind to Fas on target cells, activating apoptosis.
Immature B cells are produced in the bone marrow and undergo immunoglobulin rearrangements to become naive B cells that express surface IgM and IgD. What two ways does B-cell activation occur?
- Antigen binds surface IgM or IgD, resuling in maturation to IgM or IgD-secreting plasma cells.
- B-cell antigen presentation to CD4+ helper T-cells via MHC class II.
B lymphocytes are activated either by antigen binding surface IgM or IgD which results in a IgM or IgD plasma secreting cell OR a B-cell antigen presentation to CD4+ helper T’s via MHC Class II.
If the activation occurs in the latter way, what else has to happen to activate the B-cell after it presents antigen to the Th2 cell?
CD40 R (on Bcell) binds CD40L (on T cells), providing the second activation signal.
*Helper T then secretes IL-4 and IL-5, which mediates B-cell isotype switching, hypermutation, and maturation into plasma cells).
A collection of epithelioid histiocytes (macrophages with abundant pink cytoplasm, usually surrounded by giant cells and a rim of lymphocytes.
Granuloma.
Common etiologies include reaction to foreign material, sarcoiosis, beryllium exposure, Crohn disease, and cat scratch disease
Non-caseating granulomas (lack central necrosis)
Tb and fungal infections cause this
Caseating granulomas (central necrosis)
What do macrophages secrete that induce CD4+ helper T cells to differentiate into TH1 subtype?
IL-12
What do Th1 cells secrete, which will convert macrophages into epithelioid histiocytes and giant cells which characterize granulomas?
IFN-gamma
Present with T-cell deficiency (lack of thymus), hypocalcemia (lack of parathryoid hormone), abnormalities of heart, great vessels and face.
DiGeorge Syndrome (22q11 microdeletion): developmental failure of the 3rd and 4th pharyngeal pouches.
Characterized by defective T-cell and B-cell immunity which results from adenosine deaminase (ADA) deficiency.
SCID: Since ADA is necessary to deaminiate adenosine and deoxyadenosine for exretion as waste products, buildup of adenosine and deoxyadenosine is toxic to lymphocytes.
X-linked disease caused by mutated Bruton tyrosine kinase
Presents with recurrent bacterial, enterovirus and Giardia lamblia infections after 6 months of age.
x-linked agammaglobulinemia: disordered B cell maturation.
Avoid live vaccinations
Remember that there is no antibody to opsinize the bacteria, and no IgA to protect the mucosa (enterovirus and Giardia affect GI tract).
Common variable immunodeficiency (CVID) is characterized by low Ig due to B-cell or T-cell defects. There is an increased risk for bacterial, enterovirus and Giardia infections.
What disorders does having CVID increase the risk of?
Autoimmune and lymphoma
Most common immunoglobulin deficiency.
IgA: increased risk for mucosal infection, esp. viral; however, most patients are asymptomatic.
Hyper IgM syndrome is caused by _______.
Mutated CD40L (on helper T cells) or CD40 (on B cells).
Second signal can not be delivered to helper T cells during B-cell activation. Consequently, cytokines necessary for Ig class switching are not produced.
Low IgA, IgG, and IgE result in recurrent pyogenic infections, due to poor opsonization, esp. at mucosal sites.
Characterized by thrombocytopenia (increased bleeding), eczema, and recurrent infections (defective humoral and cellular immunity)
Wiskott-aldrich syndrome: due to mutation in the WASP gene (X-linked)
What do C5-C9 deficiencies increase the risk for?
Neisseria infection (gonorrhea and meningititis)
What will C1 inhibitor deficiency result in?
Hereditary angioedema (edema of skin and mucosal surfaces).
Nothing to inhibit complement.
Sjogren’s cancer association
B-cell lymphoma
Suspect if patient has unilateral growth of parotid.
SLE: characterized by ANA (sensitive but not specific). What antibody is specific?
Anti-ds DNA
Drug-induced lupus antibody
Antihistone antibody
Drugs that cause are hydralazine, procainamide, and isoniazid. Removal of drugs = remission of symptoms.
SLE can lead to false + syphillis test and falsely elevated PTT labs. Why?
Antiphospholipid antibody syndrome, where you have:
Anticardiolipin and lupus anticoagulant.
1 of death in lupus patients
Diffuse proliferative glomerulonephritis
Sjogren’s syndrome is lymphocyte mediated damage (type IV hypersensitivity) with fibrosis. Dry eyes, dry mouth because autoimmune destruction of lacrimal glands.
Characterized by ANA and anti-SSA and anti-SS-B. What is the target of these two anti-bodies?
Ribonucleotide proteins.
Sjogren’s is associated with other AI disorders. Which one is most common?
RA
Scleroderma is an disorder characterized by autoimmune tissue damge with activation of fibroblasts and deposition of collagen (fibrosis). Along with ANA, you will have Scl-70 antibody. What is this antibody against?
DNA topoisomeriase
What is crest syndrome?
Type of localized scleroderma.
Crest:
Calcinosis Reynaud's Phenomenon ESOPHAGEAL DYSMOTILITY Sclerodactyly Telangectasia
Note: Has Anti-Centromere antibody
If you see features of SLE, systemic sclerosis, and maybe a little bit of polymyositis mixed together, what kind of serum antibodies will you look for to help make a dx of mixed connective tissue disease?
anti-U1 ribnonuceloprotein antibodies.
There are 3 types of wound healing based on tissue regenerative capacity.
- Labile tissues: constant regeneration
- Stable tissues: Have quietscent G0 cells that can reenter the cell cycle to regenerate when necessary
- Permanent tissues: lack significant regenerative capacity.
What type of tissues fall in each?
- Labile:
Skin (basal cell stem cells)
Small and large bowel (stem cells in mucosal crypts
Bone marrow (hematopoietic stem cells. - Stable:
Liver regeneration by compensatory hyperplasia after partial resection. - Permanent: myocardium, skeletal muscle and neurons.
During wound healing, when will you get repair rather than replacement?
Repair is replacement of damaged tissue with a fibrous scar.
It occurs when regenerative stem cells are lost (deep skin cut) or when a tissue lacks regenerative capacity (after myocardial infarction).
During wound healing, when regeneration can’t occurs and repair must happen, granulation tissue occurs first. What does granulation tissue include (3 things)?
Fibroblasts (depositis type III collagen)
Capillaries (provides nutrients)
Myofibroblasts (causes wound contraction)
Note: Type III collagen will be eventually replaced with Type I collagen via collagenase (with zinc cofactor).
Type 1 collagen includes:
bONE
skin
tendons
most organs
Type III collagen includes:
Remember, it is pliable, so it includes:
Blood vessels, granulation tissue, embryonic tissue
Type II collagen includes:
CarTWOlidge
cartilage
Type IV collagen is found in the:
basement membrane
Keloids are formed from what type of collagen
Type III (pliable)–>remember type III is the type used in the initial granulation tissue of wound repair.
Enzyme used to catalyze reaction from TYPE III to Type I collagen in wound repair? What is needed as cofactor of this enzyme?
Collagenase (needs zinc as a cofactor)
Tissue regeneration and repair is mediated by paracrine signaling via growth factors. The growth factor interaction with its receptor will result in gene expression and cellular growth. Here are a few examples:
TGF-alpha TGF-beta PDGF: Fibroblast growth factor VEGF
Which of these is:
- an important fibroblast growth factor while also inhibiting inflammation?
- Important in angiogenesis?
- TGF-B (remember that when macrophages secrete this, they call off the acute inflammation and start the healing response).
- Fibroblast Growth Factor and VEGF are both important in angiogenesis.
What is the difference between primary and secondary intention when relating to cutaneous healing??
- Primary intention: wound edges are brought together (suturing of a surgical incision); leads to minimal scar formation.
- Secondary intention: edges are not approximated. Granulation tissue (fibroblasts, capillaries, and myofibroblasts), then a scar forms.
You would have delayed wound healing with infection, vitamin C, copper and zinc deficiencies as well.
Why would vitamin c, copper and zinc deficiencies cause delayed healing?
- Vitamin C:cofactor for hydroxylation of proline and lysine procollagen residues. This hydroxylation is necessary for eventual collagen cross-linking.
- Cooper: cofactor for lysyl oxidase, which cross-links lysine and hydroxylysine to form stabile collagen.
- Zinc is cofactor for collagenase, which replaces Type III collagen with Type I.
Dihiscence
Rupture of a wound, most commonly seeen after abdominal surgery.
What is the difference between a hypertrophic scar and a keloid?
Hypertrophic scar is excess production of scar tissue that is localized to the wound. Keloid is excress scar tissue that is out of proportion to the wound (Excess type III collagen, AA, classically earlobes, face and UE).
Kallman Syndrome
Defective migration of GnRH cells and formation of olfactory bulbs; Decreased Synthesis of GnRH in hypothalamus; anosmia, lack of secondary sexual characteristics. Decreased GnRH, FSH, LH, testosterone and sperm count.
FA page 525
Three phases of gastric activity are cephalic, gastric and intestinal. Which phase(s) has/have increased gastric acid secretion and which have reduced?
Cephalic and gastric: increased (release of gastrin —>H+)
Intestinal phase reduces gastric acid secretion
When doing drug trials, how do you determine the Number Needed to Harm (NNH)?
Find attributable risk:
Event rate of treatment - Event rate of placebo.
NNH = 1/attributable risk
page 52 FA
In the final step of insulin synthesis, the pancreas B-cell cleaves away a portion of the proinsulin polypeptide chain, forming insulin. What happens to the other part of proinsulin that is cleaved from insulin?
C peptide is put in secretory granules with insulin and they are both secreted in eqimolar concentrations.
Pulmonary fibrosis is a restrictive lung disease whereas COPD and asthma are obstructive lung diseases. How do people breathe in each one (rate and depth)?
Restrictive lung disease: Rapid, shallow breaths.
Obstructive: slow, deep breaths
Obstructive of what vein will cause the following symptoms:
Right slided face and arm swelling
Engorgement of subcutaneous veins on the right side of the neck?
Right Brachiocephalic vein
Note: If symptoms were bilateral, this would be SVC Syndome.
Autosomal recessive disorder caused by a deficiency in the enzyme homogentisic acid oxydase, which causes arthritis and deposits in sclera and ear cartilage. Urine turns black when hits air.
Alkaptonuria: This enzyme normally breaks down the tyrosine byproduct homogentysic acid (also called alkapton). This acculated homogentesic acid causes pigment deposits in connective tissues throughout the body.
Name that pharyngeal pouch:
Epithelium of middle ear and auditory tube
1st pharyngeal arch
Name that pharyngeal pouch: thymus and inferior parathyroid glands
3rd arch
Name that pharyngeal arch:
Superior parathyroid glands, ultimobranchial body
4th pharyngeal arch
Myasthenia gravis is associated with abnormalities of the _____________.
thymus
What is the difference between suppression and repression as relates to coping skills?
Suppression: CONSCIOUS, mature defense mechanism involving troublesome thoughts or impulses.
Repression: UNCONSCIOUS removal of disturbing psychological material from conscious awareness.
What heart abnormality is associated with Downs Syndrome?
Endocardial cushion defects (Ostium primum ASD, regurgant atrioventricular valves)
Heart defect associated with DiGeorge Syndrome.
Tetrology of Fallot and interrupted aortic arch.
What heart defect is associated with Marfan Syndrome?
cystic medial necrosis of aorta.
Heart defect associated with Turner Syndrome:
Coarctation of the aorta.
What heart defect is associated with Tuberous sclerosis?
Valvular obstruction due to cardiac rhabdomyomas. (TS = benign tumors in a lot of different tissues including brain and kidneys).
Heart problems associated with Friedreich’s ataxia.
Hypertrophic cardiomyopathy.
What is defective in kertagener syndrome?
Dynein in the microtubules, which means so movement of cilia. Infertility, recurrent sinusitis and bronchiectasis result. Is associated with situs inversis.
Most common three cancers in women?
Breast, lung, colon
Note: When looking at mortality, it is in the following order: Lung, Breast, Colon
What is the best way to prevent neonatal tetanus?
Give maternal vaccine during pregnancy. This will allow the transfer of protective IgG antitoxin antibodies across the placenta.
What is the difference between brief psychotic disorder, schizophreniform disorder and schizophrenia?
The amount of times that symptoms last.
Brief psychotic disorder: < 1 month
Schizophrenifom: 1 month - 6 months
Schizophrenia: > 6 months
What happens if there is incomplete obliteration of the processus vaginalis?
You get indirect inguinal hernia (hernia through the deep inguinal ring, but not in the inguinal triangle as with direct hernia).
BUT, if you don’t have a herniation but still have incomplete obliteration, fluid can leak into the testicles causes hydrocele of the testicle.
Fetus with flat face, abnormal ears, slanted palpebral fissures, redundant skina t nape of neck, hypotonia, pelvic dysplasia and single transverse palmar crease.
Down Syndrome (Trisomy 21)
Microcephaly, low-set ears, prominent occiput and small mandible. Clenched fist and fingers overlap. What is it?
Trisomy 18 (Edwards Syndrome)
Cleft lip and palate, polydactyly and omphlocele
Trisomy 13 (patau syndrome)
How do you attempt to prevent acute organ rejection after a transplant?
Calcineurin inhibitors: cyclosporine and tacrolimus. If in active rejection, give steroids.
In the female reproductive tract, androgens and progesterone are synthesized from cholestrol in the theca interna. Where are these androgens converted to estradiol?
The granulosa cells have aromatase, which can convert androgens to estradiol. This occurs under the stimulation of FSH.
Polyhydramnios refers to excessive accumulation of amniotic fluid and is typically related to either decreased fetal swallowing of increased fetal urination. What fetal anomalies are associated with polyhydramnios?
Gastrointestinal obstruction due to duedenal, esophageal, or intestinal atresia and ANACEPHALY.
What causes Potter’s Syndrome?
Severe oligohydramnios. You will get renal a genesis and fetal compression by the uterus, which results in fetal deformities.
Connection observed at the apices of glandular cells and consist of two closely adherent cytoplasmic membranes without an intervening space. The first component of the junctional complex.
Tight junctions
Delicate network of cytplasmic filaments that radiate from teh cell membrane to hold adjacent cells together. They are the second component of the junctional complex.
Intermediate junctions
Small, circular, adherent patches circumferentially palced around cellst hat comprise the third component of the junctional complex. They are common in stratified squamous epithelium and contribute significantly to the structural cohesiveness of tissues subject to mechanical stressors.
Desmosomes
Extend from basal surfaces of keratinocytes in the stratified squamous epithelium to attach to the basal lamina.
Hemidesmosomes.
Osteocytes have long intracanalicular processes that extend through the ossified bone matrix. These processes send signals to and exchange nutrients and waste products wtihin the neighboring lamallae via _______________ junctions. Osteocytes can sense mechanical stresses and send signals to modulate the activity of surface osteoblasts, therby helping to regulate the bony remodeling.
Gap
In a normal bell-shaped distribution, what % falls within:
1 std
2 std
3 std
1: 68%
2. 95%
3. 99.7%
Chronic granulomatous disease is an X-linked disorder resulting in the deficiency of what enzyme?
What test is used to diagnose this disease?
- NADPH oxidase (O2 —> O2- can not be done, meaning that HOCL- can not be created to kill the bacteria in the neutrophil.)
- Nitroblue tetrazoium test: If it DOES NOT CHANGE COLOR, then there IS a deficiency of NADPH oxidase.
S. aureus has an enzyme on its surface that reacts with prothrombin , which results in converting fibrinogen to fibrin. This process is believed to result in fibrin-coating of the organsims and resistance to phagocytosis. What is the molecule on the surface of S. aureus?
Caoagulase
What is the enzyme produced by clostridium bacteria that is capable of destroying erythrocytes, platelets, leukocytes and endothelial cells? It is responsible for the necrosis observed in gas gangreen (closteridium myonecrosis).
Lecinthinase, also called Phospholipase C or alpha toxin
A promoter region that binds transcription factors and RNA polymerase II during initiation of transcription. It is located appx. 25 bases upstream from teh beginning of the coding region.
TATA box
Note: The other promoting codon is the CAAT box, which is loacted 60-80 bases upstream on the 5’ end of the coding region.
What is the purpose of DNA methylation?
To silence the gene it is affecting. It is part of the epigenetic code.
- ___________________ is produced by Sertoli cells and is the physiologic inhibitor of FSH secretion.
- LH concentration is primarily controlled by levels of what hormone?
- Inhibin B: FSH stimulates the release of inhibin B from the sertoli cells of the testes.
- Testosterone (also DHEA and dihydotestosterone)==>all part of the LH feedback inhibition loop. LH stimulates the release of testosterone from the Leydig cells of the testes.
CO binds to hemoglobin with a much higher affinity than O2, thus preventing O2 binding to hemoglobin. It also reduces teh unloading from hemoglobin into the tissues.
Does CO poisoning affect the PaO2, and does it precipitate methemoglobinemia?
- No: The PaO2 (partial pressure of oxygen dissolved in the plasma) does not change. It affects only the amount of oxygen that can bind to hemoglobin. Thus PaO2 in CO poisoning is normal.
No. Methemoglobin is formed with the Fe2+ (ferrous iron) in heme is oxidized to Fe3+ (ferric iron). This results from drug exposures (dapsone, nitrites), as well as enzyme deficencies and hemoglobinopathies.
- How does CSF get from the lateral ventricles to the third ventricle?
- From the third to the fourth ventricle?
- From the fourth ventricle to the subarachnoid space?
- Interventricular foramen of monroe (lateral to third)
- Cerebral aquaduct (third to fourth)
- Lateral foramina or Luschka or Medial foramen of Magendie (fourth to subarachnoid space).
* Note: CSF is returned to the venous circulation via the arachnoid villi (granulations)
No blockage to CSF flow within the brain or brainstem, but a blockage in the subarachnoid space where flow may be restricted by fibrosis following inflammation
Communicating hydrocephalus
Hydrocephalus where CSF is not absorbed by the arachnoid villi
Normal pressure hydrocephalus
Increased CSF volume occurring in conditions of brain atrophy
Hydrocephalus ex vacuo
A condition that classically occurs in overweight young females and is related to decreased CSF outflow of the arachnoid villi
Pseudotumor cerebri
The RAS-MAP kinase pathway is a signal tranduction pathway that leads to gene transcription. RAS is a G-protein that exists in active and inactive forms.
What makes RAS inactive?
What makes RAS active?
Inactive RAS: attached to GDP
Active RAS: bound to GTP (occurs after the tyrosine kinase receptor on the membrane autophosphorylates).
Note: Activated RAS starts a phosphorylation cascade tht starts with activation of RAS kinase. This results in activation of MAP (mitogen-activated protein) kinase, which enters the nucleus to influence gene transcription.
Annular pancreas is when the pancreas encircles the descending part of the duodenumand may lead to symptoms of duodenal obstruction in neonates. Embyologically, what causes annular pancreas?
The abnormal migration of the ventral pancreatic buds.
Ventral pancreatic bud gives rise to a portion of the head, the ucinate process adn the main pancreatic duct.
What is t(15:17) associated with?
*What type of cancer and what receptor is messed up?)
The M3 variant of Acute Myelogenous Leukemia, called Acute PROMYELOTCYTIC leukemia.
The gene for RETINOIC ACID RECEPTOR alpha from chromosome 17 is transferred to chromosome 15 in a location adjacent to the PML gene. The fusioni causes an abnormal retinoic acid receptor, inhibiting myeloblast differentiation.
Abnormal epidermal growth factor receptors are associated with what type of cancers?
ERB1: Non-small cell lung carcinoma
ERB2 (aka HER2/neu): breast cancer
Defective platelet derived grwoth factor receptor plays a role in what type of cancer?
CML: Chronic myelomonocytic leukemia
Abnormal Rb gene prediposes individuals to what two types of cancer?
Retinoblastoma and osteosarcoma
In the kidney, what does the ureteric bud ultimately give rise to?
The collecting system, including the collecting ducts, minor calyces, major calyces, the renal pelvis and ureters.
In the kidney, what does the metanephric mesoderm give rise to?
Glomerulus, Bowman’s space, the proximal tubule, loop of Henle, distal tubule and the collecting tubule.
What is associated renal angiomylipoma? (Benign tumor of blood vessels, smooth muscle and fat)
Tuberous sclerosis (autosomal dominant), so will present with brain harmartomas and ash-leaf skin patches. Patient can have seizures from the harmartomas.
What is the primary site of regulation of potassium concentrations in the tubular fluid and urine?
Collecting duct.
Note: 2/3 of filtered potassium is absorbed in the proximal convoluted tubule.
20% of that filtered potassium load will then occur in the loop of henle by the Na/K/2Cl transporter.
The rest occurs in the collecting duct and depends on state of kalemia in the body.
The left kidney lies immediately deep to the tip of the ______ rib.
12th
What cells would be expected to undergo hyperplasia and hypertrophy in the event of decreased kidney perfusion?
Modified smooth muscle cells of the afferent arteriole, which secrete renin from the juxtaglomerular apparatus. These cells are located in the afferent and efferent arterioles. In the event of low perfusion, the afferent JG cells will synthesize and secrete renin.
What essential protein is necessary to promote the growth and differention of T-cells?
Calcineurin, a protein phosphatase will work on NFAT (nuclear factor of activated T-cells), dephosphorylating it. Then, the NFAT will cuase IL-2 promotion.
IL-2 stimulates growth and differential of T-cells.
What do the immunosuppressant drugs, cyclosporine and tacrolimus, inhibit?
Calcineurin, which causes upregulation of IL-2 and therefore causes T-cell differentiation.
These drugs are commonly used as immunosuppressants in kidney transplantation.
Chronic NSAID use can cause what in the kidneys?
Chronic interstitial nephritis. Usually gets better when medication is stopped.
Amphotericin B works by binding ergosterol in fungal cell membranes to form holes. It is the drug of choice for mucormycosis. Considering the side effects of this med, what should be routinely monitored?
This drug is NOTORIOUS for renal toxicity.
Severe HYPOKALEMIA and HYPOMAGNESIA
*Note: May often relay daily supplementation.
A 64-year old male hospitalized with severe abdominal pain and hypotension begins to hyperventilate. Lab testing reveals metabolic acidosis, an increased anion gap and high plasma lactate levels. This patient’s findings are best explained by a low activity of what enzyme?
Pyruvate dehydrogenase.
Hypoxia induced lactic acidosis is typically caused by low activity of this enzyme because oxidative phosphorylation can’t take place and there is a high activity of lactase dehydrogenase.
When will you see someone with renal osteodystrophy?
End-stage renal disease: Causes hypocalemia via renal retention of phosphate and decreased renal synthesis of calcitriol (1,25-dihydroxycholecalceriferol vitamin D. Both hypocalcemia and the resultant secondary hyperPTH contribute to renal osteodystrophy.
A drug used to treat intraocular pressure is also a diuretic.
What is the drug and what part of the tubule does it work?
Acetazolamide: Carbonic anhydrase inhibitor.
It works in the proximal tubule.
Note; will cause alkaline urine because CA blocks NaHCO2 and water reabsorption in the proximal tubule. If CA is block, you pee out the NaHCO2. (alkaline urine)
Aldosterone antagonist commonly used in treating class III and IV heart failure patients. It is structually similar to steroids, so can cause gynecomastia, decreased libido and impotence.
Spironolactone.
NOTE: Eplerenone is a newer and more selective aldosterone antagonist that may produce less endocrine effects.
DNA-dependent RNA polymerase that incorporates short RNA primers into replicating DNA.
Primase
Topisomerases are enzymes that relieve the resultant strains from when helicase separates and unwinds, causing supercoiling.
Another name for topoisomerase.
Gyrase
During kidney transplantation, after connecting graft and host vessels, the kidney becomes cyanotic and mottled immediately. What type of hypersensitivity is this?
Type II - There are preformed recipient antibodies against antigens on the host organ.
Type I hypersensitivity (immediate) in cases of anaphylaxis, urticaria and some forms of seasonal allergies and asthma. What is happening on a cellular level in Type I?
Antigen leads to IgE class switching on B-lymphocytes.
Type of sensitivity reaction where antibody-antigen complexes along with complement bind and attract neurophils to cause increased inflammation and tissue damage at site?
Type III: Immune complex mediated.
Graft versus host disease is a type of what kind of hypersensitivity?
Type IV: Cell mediated, caused by competent donor T-cells form a donor attack host.
Anti-GBM ab can react with the type IV collagen in the glomerular basement membrane and alveoli (hematuria and hemoptysis) This is found in Goodpasture’s Disease. On light microscope, what will you see?
What about on IF?
Light microscope: Crescents (Rapidly progressive Glomerulonephritis, Type 1)
IF: linear deposits of IgG and C3 along the glmoerular basement membrane.
What is the first way to tell if diabetes is injury the kidneys?
Microalbuminuria
HIV patient has visual problems.
What is probably causing it?
What drug do you give/
CMV-causes retinitis in AIDS patients.
Foscarnet-an analog of pyrophophate that can chelate calcium and promote nephrotoxic renal magnesium wasting. These toxicities can result in symptomatic hypocalcemia and hypomagnesemia.
What happens to the GFR and FF (filtration fraction) when you have severe vasoconstriction of the EFFERENT arteriole?
GFR: Increases (to a certain extent)
FF: Always increases.
Spike and dome appearance on electron microscopy?
Membranous glomerulopathy: most common cause of nephrotic syndrome in adults.
It can be secondary to underlying malignant tumors, infections and certain mediations. Diffuse thickening of the glomerular basement membrane (on light microscopy) without increased cellularly.
Remember, has “membranous” in the name, so is Ig mediated.
Caucasian male undergoing treatment with Amphotericin B for disseminated histoplasmosis complains of weakness and palpitations. ECG reveals frequent premature ventricular beats. What does drug toxicity of this drug cause?
Renal tubular dysfunction. So, hypokalemia and hypomagnesia cause the problem in the heart.
What does ureteral constriction or obstruciton do to the GRF and FF?
Decreases both.
Why do uric acid crystals tend to precipitate out in the collecting ducts or DCT?
This is more acidic. They will be soluble in a normal pH. They need a more acidic environment to precipitate out.
Wegener’s Granulomatosis
c-ANCA
Upper respiratory (sinus infection) Pulmonary systems (hemoptysis) Renal: hematuria (Rapidly progressing glomerulonephritis-crescentric)
Renal Blood Flow (RBF) refers tot the volume of blood that flows through the kidney per unit time and can be calculated by dividing the
RPF/(1-hematocrit)
How do you determine renal plasma flow (RPF)
RPF = PAH clearance
PAH clearance is determined by:
(urine [PAH] X urine flow rate)/plasma [PAH]
Coca-cola colored urine and facial edema after a step infection is poststreptococcal glomerulonephritis. What characteristic is most likely to affect prognosis of these patients.
Age: children recover 95% of the time.
Adults: only 60% will resolve completely.
Where will you find the most concentrated urine in the absence of ADH?
The junction between the descending and ascending limbs of the loop of Henle.
A patient presents with periorbital edema, hematuria, and a has a history of impetigo (or cellulitis or pharyngitis). What is mediating the damage to the patient’s kidneys?
Immune complexes (type III hypersensitivity). Causing poststreptococcal glomerulonephritis.
More than 60% of fluid filtered into the glomerulus is reabsorbed in the ______________, regardless of the patient’s hydration status.
Proximal tubule.
What effect does aldosterone have on the following:
Na+
N+
K+
H2O
Na+: reabsorbed
H+: secretion (follows K+)
K+: secretion
H2O: reabsorption
Alcoholic (homeless) man is brought in to the ER with vomiting and prolonged oliguria. Renal biopsy shows multiple oxylate crystals observed in the tubule lumen. What happened?
Ethylene glycol is rapidly absorbed in the GI tract and metabolized to glycolic acid, which is toxic to renal tubules, and to oxalic acid, which precipitates as calcium oxylate crystals in the renal tubules.
High anion gap and metabolic acidosis and osmolar gap are typical.
What is the normal kidney filtration fraction in a normal healthy individual?
20%
A 45-year old female with polyuria receives a vasopressin injection. Her urinary output decreases signficantly shortly afterward. Renal clearance of which of the following substances would be most significantly reduced from baseline after the injection?
Glucose Creatinine Urea Para-amino hippuric acid Calcium
Urea
Vasopressin (ADH) produces a V2 receptor-mediated increase in permeability to water and urea at the luminal membrane of the inner medullary collecting duct. The increase in urea reabsorption corresponds to a decrease in the fractional excretion of urea and a decrease in renal clearance of urea from plasma.
Which type of diuretic (loop or thiazide) are more likely to cause hypercalcemia?
Thiazide (which work in the distal convulated tubule)
They work by blocking Na-Cl symporters. Since only a small amount of Na+ reaches the distal tubules, thiazides are not as efficacious as loop diuretics.
Kimmelstiel-Wilson nodules in the kidneys indicate nodular glomerulosclerosis. What are K-@ nodules pathognomonic for?
Diabetes nephropathy
Note: ACE inhibitors and ARBs can prevent progression to diabetic nephropathy!!!
What happens to most people who experience acute tubular necrosis?
They experience tubular re-epithelization and regain renal function.
42-year-old white guy with hypertension and hematuria undergoes renal biopsy. Light microscopy reveals cellular proliferation, focal necrosis, and crescent formation of most glomeruli. On IF, THERE ARE NO IG COMPLEMENT DEPOSITS. What additional findings would you expect?
Serum anti-neurophil cytoplasmic bodies
(c-ANCA Wegeners)
p-ANCA-Churg Strauss
Note: There are not Igs to bind complement, so nothing on IF.
What kind of drug is furosemide?
Loop diuretic: inhibits Na-K-2Cl symporter in the ascending loop of henle.
What would be the common findings of the following in chronic renal failure?
- PTH
- Calcium
- Phosphate
- Calcitriol (vitamin D)
- PTH: high
- Calcium: low
- Phosphate: high
- Calcitriol: low
What happens to renal plasma flow and filtration fraction when you constrict the efferent arteriole of the kidneys?
Renal plasma flow ill decrease
FF will increase
RPF: is the volume of plasma that is delivered to the kidney per unit time.
Transitional cell carcinoma of the bladder typically presents as gross hematuria i nan elderly man. A history of smoking or occupational exposure to rubber, plastics, aromatic amine-containing dyes, textiles or leather increases the risk of developing transitional cell carcinoma. So does smoking.
n/a
Cimetidie is a H2-receptor antagonist. What is it used to treat and what is a common side effect?
Treats peptic ulcer disease: Decreases hydrochloric gastric acid production.
Gynecomastia (like spironolactone, the aldosterone antagonist(.
What vitamin increases peripheral metabolism of levadopa, decreasing its effectiveness?
B6
Acute salicylate intoxication
- Resp. alkalosis first (hyperventilation)
- Anion gap acidosis begins to develop, due to accumulation of organic acids in the blood. At high concentrations, salicylates increase lipolysis, uncouple oxidative phosphorylation, and inhibit the citric acid cycle resulting in metabolic intermediates like ketoacids, lactate and pyruvate.
Horseshoe kidney is a congenital abnormality that occurs when both kidneys are fused at the poles in early embryonic life. What does the isthmus get trapped on that prevents it from ascending to its normal place?
Inferior mesenteric artery.
Nephrotic syndrome: proteinuria, edema
What does the liver synthesize to help bulk up the blood since protein is getting secreted out?
Lipoproteins.
Inherited deficiency of alpha-glactosidase A that causes accumulations of ceramide trihexosides in tissue. The earliest manifestations are angiokeratomas, hypodirosis and acroparesthia.
- What is this disease?
- What is the patient at great risk of developing if enzyme therapy is not given?
- Fabry Disease
2. Renal failure
Ultrasound examination in utero reveals bilateral absence of the kidneys in a fetus at 24 weeks. The baby is born alive at term, but dies 12 hours after birth. What is responsible for the death?
Lung immaturity.
Renal agenesis = potter’s syndrome due to oligohydramniose. Potters is low set ears and flat face, pulmonary hyperplasia, absence of kidneys.
The most common renal malignancy is clear cell carcinoma, which arises from the renal tubule cells (usually proximal tubule). What is in the cells that makes them stain clear?
Glycogen and lipids.
Why would a person taking lithium complain of excessive thirst and urination?
Lithium-induced diabetes insipidus is the result of lithium’s inhibitory action on vasopressin in receptors in the collecting ducts.
Substance A is freely filtered in the glomeruli and reabsorbed int he renal tubules. A healthy volunteer receiving substance A has the following findings:
Inulin clearance; 100 mL/min
PAH clearance: 500 mL/min
[Plasma] A: 0/5 mg/mL
Tubular reabsorption of A: 25 mg/min
What is the expected excretion rate of substance A in this volunteer?
Net excretion for A = Total Filtration Rate - Total tubular reabsorption rate.
Total filtration rate of A =GFR X [PlasmaA]
GFR is appx. equal to inulin clearance b/c inulin is neither secreted or reabsorbed in the renal tubules. So…
Total filtration rate of A = (100 ml/min)(0.5 mg/mL) - 25 mg/min
Excretion rate of A: 25 mg/min
Diabetic ketoacidosis.
Will each of these decrease or increase in the urine?
pH
HCO3-
H2PO4-
pH will decrease: as more acidic compounds accumulate in the bloodstream, H+ excretion increases throughout the nephron.
HCO3- bicarb will be recycled, so it will decrease in the urine
H2PO4-: Increase, because there is a limit to urinary excretion of free H+ (minimum urinary pH is 4.5), so some H+ is bound by HPO4^2- and NH3 to form the titratable acids H2PO4- and NH4+ respectively. Binding of H+ by these buffers allows for the excretion of more acid without a rapid decrease in urinary pH.
Where do the most potent class of diuretics work in the kidney? (What symporter and what part of the tube?)
Loop diuretics work by inhibiting the Na+K+2Cl- symporter in the thick ascending loop of henle and effectively block Na+ and Cl- transport resulting in increased Na+, Cl- and H2O excretion.
Common side effects: hypokalemia, hypomagnesemia and hypocalcemia.
Loopes: Furosemide torsemide, bumetanide and ethacrynic acid. Used to treat pulmonary edema, venous and pulmonary congestion secondary to CHF, and peripheral edema. Note: less common side effect is ototoxicity.
What type of drug is acetazolamide?
Diuretic that works in the proximal tubule inhibiting carbonic anhydrase. Carbonic anhydrase inhibitors block the reabsorption of NaHCO3 in the proximal tubule.
Mannitol is an osmotic diuretic.
Where does it work?
Descending limb of loop of Henle and proximal tubule.
The descending limb is very permeable to water, allowing water to diffuse into the interstituim to produce a more concentration tubular fluid. This diuretic reduces the absorption of water (keeps in in the tubule to be pee’d out).
Where do thiazide diuretics work?
Distal tubule, which is almost impermable to water So, these diuretics are not near as potent.
What kind of diuretics work in the collecting duct system of the kidney?
Aldosterone inhibiting diuretics (spironolactone) and sodium channel blockers (amiloride)
Note: Both types are POTASSIUM SPARING.
A mallory weiss tear is caused from repetitive, forceful vomiting. Would a person with a mallory weiss tear be in metabolic acidosis or alkalosis?
Alkalosis.
Why would starting an ace inhibitor cause a GFR reduction?
Angiotensin II preferentially constricts the EFFERENT arteriole, thereby maintaining the GFR. When you give an ACE-inhibitor, you will have less angiotensin II, so this will promote arteriolar dilation, causing GFR reductions.
Acyclovir is a antiviral that is often used to treat herpes. If you give high dose IV acyclovir, what do you need to make sure and do along the the treatment?
Aggressive IV hydration. Acyclovir can cause crystalline nephropathy if adequate hydration is not also provided.
Where is PAH concentrention lowest in the nephron?
In Bowman’s space. PAH is not reabsorbed in any portion of the nephron, yet secretion into the tubule occurs via carrier-mediated organic acid active transport.
What will you note about glucose excretion at low loads?
What about at higher loads?
Normal renal handling of plasma glucose is characterized by complete reabsorption of low filtered loads at low plasma concentration. (You don’t pee any out).
Increasing fractional excretion of glucose is observed at high plasma concentrations.
Ischemic ATN is one of the most common causes of intrinsic renal failure (acute renal failure) in hospitalized patients. Muddy brown casts are pathognomonic for ATN. What part of the nephron is most susceptible to renal ischemia?
PROXIMAL TUBULES and thick ascending loop of henle.
It is estimated that for PAH, the extraction ratio (arterial plasma PAH minus venous plasma PAH divided by arterial plasma PAH) is near 90% at arterial plasma concentrations lower than 20 mg/dl. Once the plasma concentration of PAH is increased above this level, the extraction ration decreases progressively. What explains that?
PAH is freely filtered from the blood in the glomerular capillaries to the tubular fluid in Bowman’s space. It is also secreted from teh blood into the tubular fluid by the cells of the proximal tubule by a carrier protein-mediated process. The secretion of PAH can be saturated at high blood levels.
An 8-year old male is brought tot he doctor with a puffy face and coca-colored urine. He had experienced a skin infection three weeks ago. A kidney biopsy is performed and IF is done. What will IF show?
Granular deposits of IgG,IgM and C3 in the mesangium and basement membranes. A ‘starry sky’ appearance.
A 60-year-old male with painless hematuria is found to have a right-sided renal mass. There is no significant family history. Cytologic evaluation of the mass shows malignant cells with chromosome 3p deletion. The deletion most likely involves what gene?
VHL-Patients with both sporadic and hereditary (associated with Von Hippel-Lindau disease) renal carcinomas are found to have deletions of the VHL gene on chromosome 3p
If you see imaging of a kidney and liver full of cysts, there is a genetic problem. What is most likely mode of inheritance?
Autosomal Dominant
ADult polycystic kidney disease
Most frequent genetic cause of renal failure in adults.
If an elderly patient has a normal creatinine, would you want to decrease the dose in mediations that are renally cleared, such as digoxin?
Because elderly patients exhibit age-related renal insufficiency, even in the presence of normal creatinine levels.
Side note: Digoxin is a cardiac glycoside and toxicity will present with visual changes and GI disturbances.
These are side effects for what type of drug?
Decreased GFR
Hyperkalemia
Cough
Angioedema is a rare, but life-threatening side effect.
ACE-inhibitors (pril)
If you have an individual who is in diabetic ketoacidosis and their PaCO2 is not low, what is going on?
They are in respiratory failure. They should be breathing off CO2 in a compensatory response to the metabolic acidosis. They can do this for awhile, but eventually will have respiratory failure if they do not receive medical care.
How do you determine filtration fraction (FF) if you are given the GFR (which can be inulin rate), renal blood flow (RBF) and Hct?
FF=GFR/[(1-Hct)(RBF)]
- Where does the highest tubular fluid osmolarity occur in the nephron? (High osmolarity = most concentrated fluid)? Note: This question is referring to when there is no secretion of vasopressin.
- Where does the lowest osmolarity (most dilute fluid) occur when ADH is secreted?
- Osmolarity around 1200 at the bottom of the loop.
2. Osmolarity about 100 in the distal convoluted tubule.
What will you see on electron microscopy if you have hematuria, mild proteinuria and ocassional RBC casts following facial impetigo three months prior on electron microscopy?
Discrete subepithelial humps on EM.
On IF, you will see “lumpy-bumpy” Ig deposits (not linear). These desposits are of IgG and C3.
What type of diuretic (class and name) has the toxicity of pulmonary edema.
Osmotic diuretics-mannitol
Class of diuretics used to treat edema secondary to heart failure, renal disease or liver disease?
Thiazide diuretics & Loop diuretics (furosemide, bumetanide, ethacrynic acid)
Side effects: Hypokalemia and hypomagnesemia
Where do the loop diuretics, like bumetanide, work?
Inhibit NaK2Cl symporters in the ascending loop, so these will be excreted (along with water). Commonly used to treat pulmonary edema.
Hypokalemia, Hypomagnesmia and hypocalcemia are side effects.
Triamterene is what kind of diuretic?
Potassium sparing that works in the distal tubule/collecting duct blocking Na+ channels.
Characterized by facial edema with massive proteinuria. It is the most common cuase of nephrotic syndrome in children 2-8. It may be associated with respiratory infections, immunization, or atopic disorders (urticaria). Responds to corticosteroid treatment.
- What is the disease?
- How would you get a definite diagnosis? (IF, Light microscopy, electron microscopy)
- Minimal change disease.
- EM-effacement of foot processes.
Remember that Focal Segmental Glomerular Sclerosis also has effacement of foot processes, but occurs in older people and does not respond to steroid therapy.
Note: NOTHING shows up on IF! No complement or Ig deposits. Weird!
Three things that determine the amount of molecules that can cross a semipermeable membrane.
- Difference of the molecule’s concentration across the membrane.
- Total membrane surface area
- Solubility of the substance.
Note: Diffusion is inversely proportional to the total membrane thickness and the molecular weight of the molecule.
What happens to the GFR, RPF, and FF in the case of a severely hypovolemic individual with a BP around 90/60?
(Do each go up or down)
RPF: Down a lot (low blood volume)
GFR: Down, but not as much. (B/C the auto regulatory mechanisms kick in (renin and constriction of efferent arterial).
FF is a function of GFR/RPF, so since RPF goes down a lot more than GFR, the FF will increase.
What structure is at risk of injury during pelvic surgeries (particularly cervix and hysterectomies)?
Uterine aa. can be accidentally ligated. This would result in hydronephrosis.
Acute tubular necrosis has three stages:
Initiation stage: ischemic injury to renal tubules precipitaed by hemorrhage, acute MI, sepsis, surgery, etc.
Maintenance stage: Decreased urine output, fluid overload, increasing creatine/BUN
Recovery Phase: Gradual increase in urine output leading to high-volume diuresis. Electrolyte abnormalities may include decreased concentrations of K, Mg, PO4, and Ca due to slowly recovering tubule function.
What might you see hyperkalemia?
When will you see hypokalemia?
Hyperkalemia: Maintenance stage
Hypokalemia: Recovery stage
During the recovery stage (polyuric phase) of ATN, patients can become dehydrated and can develop severe hypokalemia due to high volume, hypotonoic urine.
Pathognomonic for ATN–>muddy brown casts
Man has muscle weakness and periodic headaches. He has a bp of 200/120. He has high renin AND high aldosterone. Where is his tumor?
Juxtaglomerular cells in the kidney (which synthesize and secrete renin)
A patient has a transplant and then about three weeks later starts feeling generalized malaise. A histopathologic image of the transplanted kidney shows lymphocytic infiltration of the renal parenchyma. What type of hypersensitivity reaction is this?
Cell-mediated hypersensitivity (Type IV-delayed type)
How are Anti-CD3 antibodies (such as muromanab-CD3) useful clinically?
They inhibit T-lymphocytes, which is useful in the treatment of acute rejection in patients with kidney, heart and liver transplants.
Note: CD4+ Th lymphocytes express MHC class II receptor and IL-2 receptors. IL-2 receptor stimulation induces T-lymphocyte proliferation. CD3 is an antigen required for the proper function of T-cell receptors.
Why might an individual develope a varacocele or any other type of clot if they have nephrotic syndrome?
They have lost a lot of protein (albumin, antithrombin III, etc). The loss of factors that prevent clotting (antithrombin III allows for clotting to take place).
Which occurs in adults versus newborns?
- Autosomal dominant PKD
- Autosomal recessive PKd
- Adults - AD
2. Babies - AR
In post glomerular strep glomerulonephritis, you will see subepithelial “humps” on EM. What are these made of?
IgG, IgM and C3
Medullary sponge kidney (MSK) is a relatively common and benign congenital disorder characterized by cystic dilatations of the medullary collecting ducts. Cysts usually do not involve the cortex. What is the most common complication of this disease?
Kidney stones
You have to know the chart with PAH, creatinine, inulin, urea, Na/K+, HCO3, a.a. and glucose.
N/A
Nephrotic syndrome where a child might be slightly puffy and can have proteinuria, but the proteinuria is predominantly albumin. What is this disease?
Is it tubular, functional ,selective, or isolated?
Minimal change disease
Selective proteinuria - albumin!
Antibodies detected in the serum that react to the alpha 3 chain of Type IV collagen.
- What does this patient have?
- What are the symptoms?
- Goodpasture syndrome - develop RPGN (rapidly proliferating glomerulonephritis).
- Hemoptysis (because ab reacts against basement membrane in alveoli)
Hematuria (reacts against basement membrane in glomerulus), oliguria.
Note: Linear IgG and c3 deposition on IF
How might you distinguinish between PSGN and IgA nephropathy?
Post strep glomerulonephritis will occur appx. 3 weeks after the infection. You will see subepithelial humps of IgM, IgG and C3 on EM). Grainy IF.
IgA (which the most common type of nephropathy) will occur TWO TO THREE DAYS after URI. Dx made via detection of IgA deposits in mesangium of glomeruli on IF.
Note: If you have IgA nephropathy with extra renal symptoms (ab pain, purpuric skin leasions), the dx is Henoch-Schonlein purport.
A 7-year old boy with 2-day history of colicky ab pain develops bloody stools and his urine appears red, too. PE reveals palpable skin lesions on his buttocks. What additional finding with be most consistent with this patient?
Class signs of Henoch-Schonlein purport (the most common vasculitis in children)
- GI tract (severe intermittent ab pain)
- Kidneys (IgA nephropathy)
- Skin (palpable purpura)
- Joints: self-limited migratory arthralgias and arthritis most commonly seen in the large joints of the LE.
What part of the nephron is normally IMPERMEABLE TO WATER?
Ascending limb of loop
Minimal change disease is a nephrotic syndrome where the main protein lost is albumin. What is the current theory of how this occurs.
Loss of negatively charged components in the glomerular basement membrane. The loss of negative particles destroys the negative-negative repulsion between the GBM and albumin.
The research division of a large pharm company focuses their efforts on studying renal tubule transport proteins. A substance is identified that specifically and completely inhibits glucose transport in the proximal renal tubules. In a healthy volunteer receiving this substance, glucose clearance will best approximate the clearance of what substance?
Inulin
What does this describe:
Easy fatigability, constipation, back pain, and azotemia in an elderly patient. On kidney biopsy, large eosinophilic casts are seen in tubular lumen.
The casts are composed of Bence-Jones proteins.
Multiple Myeloma
Crescent formation on light microscopy is diagnostic for rapidly progressing glomerulonephritis. What do crescents consist of?
Glomerular parietal cells, monocytes and macrophages, and abundant FIBRIN.
Note: Crescents eventually become sclerotic, disrupting glomerular function and causing irreversible renal injury.
Characterized by a triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia.
HUS (Hemolytic-uremic syndrome), which is a common cause of acute renal failure in children. It is associated with shiga toxin-producing organisms like E. Coli and Shigella dysenteriae.
Where does renal cell carcinoma (clear cell type) typically originate?
Proximal renal tubules.
What causes diplopia, dystonia, and dysphagia?
Botulinum toxin, which you can get from wounds or home-canned food consumption.
Prevents release from ACh from nerve terminals at the NMJ, thereby preventing muscular contraction.
Where are serotonergic (serotonin-releasing) neurons found in the CNS?
What do lesions in these areas cause?
The raphe nuclei of the brainstem (midbrain, pons and medulla). The axons from these cells bodies project widely throughout the CNA to synpase on structure such as the cerebral cortex, thalamus, hypothalamus, cerebellum, hippocampus, and spinal cord.
- Lesions cause insomnia and depression. These neurons play a role in the sleep-wake cycle and the patient’s level of arousal.
The caudate nucleus and the putamen from the striatum in the brain which functions in motor activities. In what disease will there be a loss of cholinergic and GABA-releasing neurons in the striatum?
Huntington’s
What do the neurons in the red nucleus, which is located in the anterior midbrain, participate in?
The motor activities of the upper extremities.
The nucleus basalis of Meynert houses the cell bodies of cholinergic neurons. In Alzheimer’s disease, these neurons secrete in adequate amount of ______________.
acteycholine.
Basic interviewing techniques include facilitation, reflection, confrontation, support, empathy, silence and direct and indirect questioning. What is the primary difference between support and empathy?
Support involves expressing concern independent of understanding. With empathy, the physician expresses understanding and varcarious experiencing of a patient’s situation.
A resident is belittled by his attending on rounds who later angrily berates his medical student. What mechanism is this?
Displacement
Acute stress disorder and PTSD present with identical symptoms (recurrent nightmares and flashbacks, potential memory loss, and exaggerated startle response). What is the difference between the two?
Acute stress disorder can last no more than 4 weeks. PTSD lasts longer than 4 weeks.
what defense mechanism does this describe:
Symbolically nullifying an unacceptable or guilt-provoking thought, idea or feeling (by confession or atonement)
Undoing
Mature defense mechanism that converts unacceptable feelings or drive into more socially accepable ones.
I.e. Agressive tendencies, so they join the military.
Mad at wife, so they go run 5 miles
Sublimation
Replacement of an unpleasant or unacceptable thought or desire with its opposite.
Homosexual desires, so talk about how homosexuality is wrong.
Reaction formation
Mature defense mechanism that alleviates guilty feelings through selfless service or giving.
Altruism
Female athlete triad
eating disorder, amenorrhea, and osteoporosis
WHat does parotid gland hypertrophy along with anterior tooth enamel erosion demonstrate?
significant vomiting history (perhaps with bulimia/anorexia)
Demential, dermatitis and diarrhea
Niacin deficiency
DSM-IV criteria
- Body weight at least 15% below normal and refusal to maintain normal.
- Amenorrhea for three months.
- Body image distortion
- Fear of gaining weight or becoming fat despite being underweight.
Anorexia nervosa
Withdrawal from this drug is described as “flu like”.
Includes abdominal pain, nausea, vomiting, diarrhea, piloerection, pupillary DILATION, diarphoresis and fevere.
Opiate withdrawal-heroine for example
Withdrawal of this drug:
psychomotor agitiation psychosis nystagmus tachycardia ataxia homicidality
PCP-This”withdrawal” is actually reintoxication due to GI tract reabsorption.
Drug withdrawal that causes hypersomnolence, fatigue, depression, suicidality and strong cravings
Cocaine
PCP, OR PHENCYCLIDINE, is a hallicinogen that works by inhibiting NMDA receptor activation, which is receptor for the excitatory neurotransmitter glutamate. What do moderate amounts of PCP cause in a person?
Feelings of detachment and distance. Additionally, it can produce ataxia, involuntary movements, exaggerated gait, NYSTAGMUS, paranoia and hallucinations (like schizo). Most users become hostile and aggressive.
Street drug that blocks the reuptake of dopamine, norepi and serotonin
Cocaine:
Causes high HR, high BP, blurry vision, tremos, twitching, chest pain, irritability, hallucinations and delusions.
Illegal drugs that is a sympathomimetic stimulant that mimics the actions of norepi on the body.
Amphetamine
Can you give patient information to a loved one if asked?
Not without the explicit consent of the patient. , which should be documented in the patient’s chart.
Eating disorder characterized by binge-eating and either restrictive or purging compensatory behaviors.
Bulimia nervosa:
If patient is <85% of ideal BMI, this would be anorexia nervosa instead of bulemia.
What does this describe:
mild eurphoria with laughing behavior, slowed reflexes, dizziness, impaired coordination, and short term memory loss.
Rapid heart rate and CONJUNCTIVAL INJECTION are the two most immediate symptoms.
Marijuana use.
Remains in tissues for a significant amount of time and can be detected up to 30 days after use.
SSRI inhibitor (like paroxetine) is considered a first line therapy for both generalized anxiety disorder and panic disorder.
However, SSRI’s take about 4 weeks to notice any therapeutic effect. Benzos can be given in the interim. There are short, intermediate and long-term benzos. Which category do each of the fall into?
Chlordiazapoxide Diazepam Triazolam Loarazepm Fluazerpam
Short: Traizolam
Intermiediate: Lorazepam
Long: Diazepam, Flurazepam, and Chlordiazepoxide
**Triazolam is a benzo that can be useful for treating insomnia in patients employed in a mission-critical positions, as its short half-life minimizes undesirable daytime side effects.
Major depression is diagnosed when at least 5 of the following symptoms are present for at least two weeks. (one of them must be depressed mood or anhedonia (inability to find pleasure in things you used to enjoy). What are the list of symptoms?
SIGECAPS
Sleep disorder Interest deficit Guilt Energy deficit Concentration deficit Appetite Disorder Psychomotor retardation or agitation Suicidality
Dysthmic disorder is a chronic, low-intensity mood disorder that responds well to antidepressant medications. Its symptoms are less severe than those of major depressive disorder. How long must the symptoms be present for a diagnosis to be made?
at least 2 years.
Unconscious manifestation of neurologic symptoms when pathophysciological explanations for the symptoms cannot be found. it occurs more commonly in women and often occurs after a significant life stress.
Conversion disorder
Causes of erectile dysfunction:
Psychogenic stressors (marital problems)
Performance anxiety or depression
Medications (SSRIs and sympathetic blockers like clonidine, methydopa and beta blockers)
Vascular or neurological impairment (would not get morning wood)
Genitourinary trauma
What is the difference between suppression and repression as defense mechanisms?
Suppression: intentional withholding of distressing unconscious material. Mature defense mechanism.
Repression: Unconscious removal of disturbing psychological material from conscious awareness. (i.e. adult who was sexually abused as a child and does not even remember until they see a movie involving sexual abuse).
If you suspect elder abuse, you get ask anyone else to leave the room and ask waht three questions?
- Do you feel safe where you live?
- Who prepares your meals?
- Who handles your checkbook.
Note: Clinicians have ethical and moral obligations to report elder abuse, neglect and exploitation. If there is reason to suspect abuse or neglect, the patient should be interviewed alone to avoid intimidation by possible abusers.
Defense mechanism:
Unconscious belief that people are either wholly good or wholly bad.
Splitting
borderlines have this alot.
A worker accusing his boss of having sexual desires fro him when the worker himself has the sexual desire.
Projection
Defense mechanism:
Former smoker vigorously enforcing a smoking ban.
Reaction formation.
Defense mechanism
A patient with sexually explicit thoughts becoming a sex therapist.
Sublimation
Throwing a tantrum
Acting out
Suppressing one’s feelings by thinking about the problem. Example: a surgeon who avoids his feeling of failure after a patient dies by thinking about every step of the surgery in meticulous detail.
Intellectualization.
Delirium vs. Dementia
Onset- Consciousness Course: Prognosis Memory impairment
DELIUM onset: Acute Consciouness: impaired Course: Fluctuating Prognosis: Reversible Memorty impairment: Global
DEMENTIA: onset: gradual Consciouness: Intact Course: Progressive decline (think Alz) Prognosis: irreversible Memory: remote memory spared.
In an emergency situation, if there is any doubt int he clinician’s mind concerning the wishes of a patient who is Jehovah’s Witness, what the best course of action?
Treat according to accepted standard of care. In an emergency, the physician should ALWAYS provide potentially life-saving therapy to a minor.
In a non-emergent setting, what do you do if there is a language barrier with a patient (either foreign language or patient is deaf)?
Always used a trained, objective interpreter!
No friends, no writing things down, no checklist, etc.
What is the most common medical cause of daytime sleepiness in the U.S?
Obstructive sleep apnea: occurs due to poor oropharyngeal tone and results in daytime sleepiness, MORNING HEADACHES, and DEPRESSION.
A 54 year old man with insulin-dependent diabetes mellitus visits his physician for a routine fu. His HbA1c is 11%, way above his goal. Although the patient is resistant to change his regimen, the physician increases his dose of insulin and insists on tighter diet control. For the next several months, the patient either arrives late for his appointments or cancels them. What defense mechanism is he exhibiting.
Passive aggressive behavior: expressing hostility toward his physician in a passive manner by missing his appointments.
Where would you find the enzyme elastase in the lungs?
Macrophage lysosomes and in the large, azurophil (or primary) granules of neutrophils.
Normally, elastase release from infiltrating neutrophils and macrophages is balanced by the antielastase activity of serum alpha1 antitypsin. Excess elastase activity in lung acini is thought to be a major factor in the development of centriacinar and panacinar emphysema.
Constitute over 95% of the epithelial lining of the alveoli. These end-differentiated squamous cells not known to be a major source of alveolar fluid secretory products.
Type I Pneumocytes
Dipalmitoyl phosphtidycholine. What is it?
Phospholipid that is secreted from TYPE II pneumocytes. It is the major component of pulmonary surfactant.
What type of cells are the germ cells in the alveoli of the lung?
Type II pneumocytes
Where are clara cells found?
Terminal respiratory epithelium.
They are not affiliated, secret Tory constituents of the terminal respiratory epithelium. They secrete Clara cell secretory protein (CSSP), which inhibits neutrophil recruitment and activation.
Do bronchioles of the lung have goblet cells?
No, bronchioles terminal bronchioles respiratory bronchioles and lung acini generally lack goblet cells.
What drug increases the peripheral metabolism of levodopa and decreases its effectiveness?
Vitamin B6
Cimetidine is a histamine-2 receptor antagonist that decreases hydrochloric gastric acid production. What can submitted Dean cause?
Gynecomastia, and this is a very frequently asked USMLE step one question.
Most patients with hyperthyroidism in the United States are treated with ablating doses of radioactive iodine. The concentration of iodine levels with in the thyroid gland is much higher compared to anywhere else in the body because thyroid follicles transport inorganic iodide against a concentration gradient. What drugs do you want to make sure and not use prior to ablating with iodide because they will decrease the effects of therapy by competitive inhibition.
Anion inhibitors (perchlorate and pertechnetate). These drugs block ioside absorption by thyroid gland via competitive inhibition.
How do drugs like methimazole and propylthiouracil treat hyperthyroidism?
These thionamides inhibit thyroid peroxidase.
What drug is known to cause Ebstein’s anomaly in infants exposed in utero?
Lithium, which is a common drug used to treat bipolar disorder.
Epstein’s anomaly includes apical displacement of the tricuspid valve leaflets, decreased right ventricular volume, and atrialization of the right ventricle.
There are three phases that classically stimulate acid secretion within the stomach. Cephalic, gastric, and intestinal.
What stimulates the cephalic and gastric phases?
The cephalic phase is mediated primarily by cholinergic and vagal mechanisms, and is triggered by the thought, sight, smell, and taste of food. The gastric phase is mediated by the presence of gastrin, which stimulates histamine secretion and therefore indirectly acid secretion, and his triggered by the chemical stimulus of food and distention of the stomach.
Note: The intestinal phase is initiated when protein containing food enters the duodenum, but this phase plays only a minor role of stimulating gastric acid. In fact, intestinal influences are effective in down regulating gastric acid secretion after a meal.
And gastric function, the ileum and colon-released peptide YY, which binds to receptors on the endocrine cells described as enterochromaffin like cell which counteracts be cephalic and gastric phases of acid secretion by inhibiting gastrin stimulated histamine release from ECL. What other factors inhibit acid secretion?
Somatostatin and prostaglandins
83 month old male undergoes surgery for a sublingual math that seems to impair his breathing. The event is brought to the ER several weeks after the surgery with lethargy, breathing problems, constipation, and dry skin. what embryologic process failed?
Migration.
Failure of migration of the thyroid gland can called lingual thyroid. Surgeons should be careful when removing any mass along that thyroglossal duct usual path, as the mass could be the only thyroid tissue present in the patient.
The classical complement pathway can be activated after C1 by either IgM or IgG. Which one is more effective at activating complement, and why?
IgM, because it circulates in pentameric form, whereas IgG circulates in monomeric form. The C1 module binds Fc portion of the heavy immunoglobulin chain in the region near the hinge point.
What will the levels of serum calcium and parathyroid hormone be like in an individual here is in renal failure?
Serum calcium will be low, and parathyroid hormone will be high.
Deficiency of 1-alpha hydroxylase in the kidney will prevent Vitamin D from getting it its active form (1, 25-dihydroxy Vitamin D). So, low calcium. The compensatory response is high PTH.
What neurotransmitter is implicated in opioid tolerance?
Gluatmate: binds and activates NMDA receptors, which can phosphoyrlate opioid receptors, including NO levels that ultimately leads to opioid tolerance.
What nerve roots are associated with saddle anesthesia (weakness in butt and perianal area), as well as loss of reflex around the ass pipe?
S2-S4
Gastric cancer tends to metastasize to one of three different areas. What are those?
Ovaries: Krukenberg tumor (mucus producing cell in the ovary)
Sister Mary Joseph nodule: periumbilical region
Virchow’s node: left supraclavicular sentinel node
Where are the are the osmoreceptors and baroreceptors that will activate the synthesis of ADH?
Osmoreceptors: Hypothalamic nuclei
Baroreceptors: carotids and atria
Note: If there is damage to these areas, you will get central diabetes insipidus. If you give the person exogenous ADH, their urine mOsm/L will go up. If it is nephrogenic DI (the kidney doesn’t respond to ADH in the collecting duct), the mOsm/L will NOT go up. This is how you differentiate between the two.
What adrenergic receptor causes constriction of the peripheral vasculature?
What adrenergic receptor causes vasodilation of the peripheral vasculature?
- Vasoconstriction: alpha-1
- Vasodilation: beta-2
Note:
Alpha-a also causes contraction of the internal urethral sphincter of the bladder, and contraction of pupillary dilator muscle (mydraisis-or dilation)
Beta-2 also causes bronchodilitation of the bronchi, and uterus relaxation.
What adrenergic receptor inhibits uterine contractions?
Beta-2 (tocolysis of uterine)
What adrenergic receptor causes contraction of the ocular pupillary dilator muscle, resulting in pupillary dilation?
Alpha-1
Langhans giant cells are characteristic of the caseating granulomas associated with M. Tuberculosis infection and have multiple nuclei preferably organized in the shape of a horseshoe. What are these granulomas composed of?
Macrophages, which are activated by CD4+ Th1 lymphocytes.
What is the primary purpose of CD8+ T lymphocytes?
Orchestrate the death of virally infected cells.
Radiation therapy is often used for cancer. How does radiation therapy shrink cancer tumors? Two ways.
Induces DNA damage through DNA double-stand fractions.
Formation of free radicals.
Polycythemia vera presents with dizziness, headaches, and Proadis after showering. What is the most likely cause of polycythemia vera?
Increased bone marrow sensitivity to growth factors (erythropoietin and thrombopoietin) due to a JAK2 mutation
Rate limiting enzyme in the urea cycle?
Carbamoyl phosphate synthestase I (CPSI), which is activated by N-acetylgultamte.
Where do the nitrogen atoms in the urea molecule from? (2 places?
NH3 and aspartate
What is a major risk of neisseria gonorrhea and chlamydia?
Infertility. Both of these bacteria can cause pelvic inflammatory disease which can lead to scarring of the fallopian tubes.
Where is ribosomal RNA synthesized?
In the nucleolus
If a patient in diabetic ketoacidosis has facial pain, headache, and black necrotic eschar in the nasal cavity:
- What do ou need to do to diagnose it?
- What is the likely diagnosis?
- How do you treat?
- Mucosal biopsy
- Mucormycosis-will see broad nonseptate hype with right angle branching.
- Surgery and Amphotericin B
WHat does this describe:
Neontal defects of the head (microcephaly, MR)
Eyes (cataracts)
Ears (Deafness)
Heart/CV (patient ductus arterioles, peripheral pulmonic stenosis
Congenital rubella syndrome.
To decrease the risk of this syndrome, the CDC currently recommends the vaccination of children and NON-PREGNANT females of childbearing age with live, attenuated rubella virus vaccine.
A 20-year-old male is evaluated for trimmer and gait instability. Laboratory studies revealed elevated serum transaminases. A serum ceruloplasmin concentration decreased what medication do you use to treat this patient?
Penicillamine.
This is Wilson’s Disease, which involves an excess of non-ceruloplasmin-bound serum copper, leading to injurious accumulation of this element in the liver, CNA lenticular nucleus and cornea. Chelation therapy with penicillamine is indicated.
Rubella typically presents with a low-grade fever and maculopapular rash. The rash spreads from the face to the chest to the trunk and extremities overtime. Usually over 48 hours. If a woman is pregnant, what is she at risk for developing? And what is the fetus at risk for developing?
Mom: polyarthralgia
Baby: deafness, cataracts and cardiac malformation.
In the lungs, what happens to perfusion as you move from the apex to the base of the lungs? What happens to ventilation as you move from the apex to the base?
Think: Gravity
Perfusion (Q) increases A LOT.
Ventilation (V) increases A LITTLE.
For this reason V/Q ratio DECREASES from apex to base.
What drugs will induce P450?
What drugs will inhibit P450?
Inducers of P450: Barbituates, RIFAMPIN, CARBAMAZEPINE, GRISEOFULVIN, CHRONIC ALCOHOL
Inhibitors: Isoniazid, cimetidine, macrolides, azole antifungals, grapefruit juice.
Hydralazine and minoxidil are drugs used to prevent severe hypertension that is resistant to other drugs.
What is its mechanism of action and side effects?
Mechanism: Arteriolar vasodilation
Side effect: because there is significant vasodiation in the arterioles, the baroreceptor mediated activation of the sympathetic system is activated. This results in increased heart rate, increased renin activity, resulting in SODIUM AND FLUID RETENTION!
Renal cell carcinoma (both hereditary and sporadic) are associated with this mutation.
VHL-There are deletions of the VHL gene on chromosome 3p.`
Retinoblastoma and Osteosarcoma mutation association
RB anti-oncogene-Chromosome 13
Dark, intraellular inclusions that stain with crystal violet?
Heinz bodies–>G6PD deficiency–>usually becomes known after a stressor (such as malaria prophylactics)
What does this describe:
Hypogonadism
Eunuchoid habitus (underdeveloped sexual organs where sexual hormones are not produced)
Small firm testes
Genotype 47 XXY
Klinefelter syndrome
Note: You will have LOW serum testosterone and LOW sperm count, but you will have high LH and FSH due to loss of feedback inhibition.
Severe retrosternal pain that radiates to the back is the classic presentation of an aortic dissection. What is thought to be the initiating process in a dissecting aortic aneurysm?
Intimal tear.
A patient comes in with flulike symptoms or chronic pneumonia. Tissue samples showed spherules containing endospores. What is your diagnosis?
Coccidiodes immitus
Fungus that commonly causes this pulmonary disease in immunocompromised patients. In tissue specimens, it is seen as septate hyphae that branch at 45° angles.
Aspergillus fumigatus
Round yeast with broad based budding.
Blastomyces
Why do individuals with Crohn’s disease develop gallstones?
Decreased bile acid reabsorption in the terminal ilieum and its loss via feces increases the lithogenecity of bile. Cholesterol precipitates informs gallstones.
What is the most common hepatic neoplasia?
Metastatic liver cancer from either the breast, lung, or colon. This is 20 times more frequent than hepatocellular carcinoma. Note that with metastases, the liver will have multiple nodules throughout. Even with significant metastatic involvement, patients may have no clinical or laboratory signs suggestive of hepatic insufficiency until their cancer gets really bad.`
What are the risk factors of hepatocellular carcinoma?
Histories of cirrhosis and for infection with hepatitis B or C.
Niemann pick disease is an autosomal recessive disorder that affects patients in their first year of life. What enzyme is deficient in this disease that causes foamy histiocytes?
Sphingomyelinase-causes abnormal accumulations of sphingomylin in phagocytes.
Autosomal recessive condition in which a deficiency of the enzyme B-hexosaminidase A causes Gm2 ganglioside to accumulate within neurons
Tay-Sachs
834-year-old male is found to have an intracranial tumor. Many cells within the tumor demonstrate outdated uptake of bromodeoxyuridine, a thymidine analogue. The finding most likely suggest that the tumor has what characteristic?
High grade: these tumors are displaying cellular and nuclear pleomrophism and a high number of mitoses. the high uptake indicates there a lot of cells in the S cycle getting ready to divide.
Note: Staging of brain tumors is not that important because these tumors rarely go outside of the brain AND even a tiny tumor can compress a vital center and be lethal.
What class of drug does this describe:
Causes hepatocytes to increase their LDL receptor density as ameans of increasing their uptake of circulating LDL
Statins
Testes drains to what lyphh nodes?
Scrotum to what lymph nodes?
Testes: para-aortic nodes
Scrotum: superficial inguinal lymph nodes
What disorder:
- Recurrent skin and resp infection
- Light skin and silvery hair
- Horizontal nystagmus
- Peripheral blood smear demonstrates GIANT CYTOPLASMIC GRANULES in neutrophils and monocytes.
Chediak-Higashi Syndrome.
Defect in neurtrophil phagosome lysosome fusion.
Hormone responsible for gallbladder contraction that is made in the duodenum and jejunum in response to fatty acids and amino acids.
Cholecystokinin (CCK)
How does decreased levels of CCK cause biliary sotnes?
CCK is responsible for gallbladder contractility. So, if there is no contractility, there is stasis. Stasis=stones.
What hormones does somatostatin inhibit?
secretin, CCK, glucagon, insulin and gastrin
Why does an individual become “lactose intolerant” after a battle with a stomach bug (like rotavirus)?
The lactase enzyme (B-galactosidase) is concentrated in the brush border of the epithelial cells of the small intestine. If these cells are lost, then there is a lactase deficiency. Remember lactose = galacto syl B-1,4-glucose)
Baby has not been feeling well, has mild jaundice, an enlarged tongue, general hypotonia, and umbilical hernia.
Hypothyroidism: FLOPPY BABY.
Need to treat stat or baby is going to develop profound and irreversible MR.
Mousy body odor, fair skin MR and developmental delay
PKU (deficiency of phenylalanine hydroxyase that leads to inability to metabolize phenylalanine.
What type of drugs are best to deal with the negative symptoms (decrease in emotional range, poverty of speech, loss of interest in living) of schizophrenia?
Atypical (2nd gen) neuroleptics (clozapine, risperidone, olanzapine, quetiapine). These are ATYPICAL antipsychotics and improve both positive and negative symptoms of schizophrena.
Birth defect caused by valproate?
Meningocele or neural tube defect. Valproate inhibits intestinal folic acid absorption.
Major virulence factor of strep pyogenes. It inhibits phagocytosis and complement activation, mediates bacterial adherence, and the target of type-specific humoral immunity to S. pyogens.
Protein M
_________________ is a glucose sensor within pancreatic beta cells. Inactivating mutations of the enzyme result in mild hyperglycemia that can be exacerbated by pregnancy.
Glucokinase
Injury to what cranial nerves will make a person unable to tolerate everyday sounds?
VII
Stapedium muscle is innervated by the stapedius nerve, which is a branch of the facial nerve.
What the typical method of contracting tetanus?
Wound–>retrograde transport up motor neuron where it causes inhibition of inhibitory interneurons and unregulated firing of primary motor neurons.
Clostridium tetani is responsible for tetanus, a toxin-mediated disease that causes uncontrolled muscle spasms and respiratory failure.
What virus takes this route:
wound—>neuron axons—>salivary glands
Rabies virus.
Food—>systemic circulation—>meninges.
What bacteria takes this route?
Listeria monocytogenes: Gram + food born pathogen that causes meningitis in neonates and immunocompromised patients.
What is the best drug to use for patients with both absence and associated tonic-clonic seizures?
Valproate for BOTH.
If it is just absence seizures alone, use ethosuximide.
How is depolarization (phase 0) of a cardiac pacemaker cell different from a non-pacemaker cell (cardiomyocytes and purkinje fibers)
Pacemaker: depolarization is due to Ca2+ rushing in.
Non-pacemaker: depolarizaiton is due to inward sodium current.
What kind of staining uses aniline dye (carbolfuchsin? What type of organisms does this stain?
Acid-fast stain: Used to stain organisms that have mycolic acid present in their cells walls.
It stains mycobacterium and some nocardia species.
On gram + or gram - bacteria:
Teichoic acid
LPS
- Teichoic acid: Gram + (antigenic target for human immune system and antigenic determinant for organism identification in the lab)
- LPS: gram -: component of out cell envelope
Why do patients with tetraology of fallot squat during episodes of severe cyanosis?
This decreases the right to left shunt (squatting increases the total systemic vascular resistance).
What side effect might the combination of statins + fibrates (atorvastatin and gemfibrozil) cause?
Myopathy. Note that stain use is also associated with hepatoxicity.
The combination of fibric acid derviatives (anticholesterol drug) and bile acid resins (cholestyramine) cause?
Gallstones (increased cholesterol int he gallbladder)
Most common infectious agents in neonatal meningitis?
Group B strep, E. coli and Listeria monocytogenes
Most common infectious agent that causes meningitis in children and teens?
Neisseria meningitis
Goes in through nose, gets in blood, then goes into meninges.
What is the MCC of meningitis in adults and elderly?
Strep pneumoniae
Why is it highly encouraged to get children vaccinated against H. influenza?
It can cause meningitis in nonvaccinated infants.
Most common virus that causes meningitis?
Coxsacievirus (children: fecal-oral)
Who gets a fungal meningitis?
Immunocompromised people.
Where do you do a LP?
Between L4 and L5 (spinal cord ends at L2, but CSF goes down to S2)
What kind of meningitis?
-Neurophils with decrease CSF glucose
Bacterial:
Group B strep, e.coli, listeria (neonates)
N. meningitis (children)
Strep pneumoniae (elderly and adults)
H. influenza (non vaccinated infants)
What kind of meningitis:
In CNS
Lymphocytes and normal glucose
Viral
What kind of meningitis
In CNS
-Lymphocytes and low glucose
Fungal
A left side mass compressing the renal vein will most like cause what?
Varicocele (b/c the testicular vein drains into the left renal renal vein ). Note: On right side, test. vein drains into the inferior vena cava, so a mass on that side would not cause varicocele.
If you have overuse of diuretics, are you more likely to be acidotic or alkalotic?
In alkalosis.
Diuretics cause Na+ and water reabsorption at the expense of K+ and H+, which will be excreted.
What do the following indicate:
- Bleeding time
- aPTT (activated partial thromboplastin time)
- Prothrombin time
- Bleeding time: platelet hemostatic function.
- aPTT: Defect in INTRINSIC coagulation system.
- PT: Indicates defect in EXTRINSIC system at a step not shared with the intrinsic system (Factor VII)
WHat do these chemicals have in common?
Leukotriene B4, H-HETE (the leukotriend precursor, complement component C5a and IL-8?
They all induce chemotaxis and phagocytosis in neutrophils.
Note: IL-8 is released by macrophages.
In a neonate, this triad is associated with what?
- Hydrocephalus
- Intracranial calcification
- Chorioretinitis
Toxplasmosis (in utero infection because it is transmitted transplacentally).
Expecting mothers should avoid cat feces to help prevent exposure to toxoplasma.
Sullfhydryl group supplementation (N-acetyl cystein) can be used to treat what kind of pharmaceutical toxicity?
Acetaminophen
N-acetyl cysteine (NAC) acts as a glutathione substitute and binds to the toxic metabolite. NAC also provides sulfhydryl groups to enhance the non-toxic sulfation elimination of acetominaphen.
Note: In therapeutic doses, tylenol is metabolized by the liver and glucoronide conjugation. When this system is overwhelmed, more goes to the c-P$%) pathway and a toxic metabolite is formed (NAPQI). This can cause hepatocellar injury and centrilobular necrosis.
Patient eats fish and then goes to ED complaining of weakenss, dizziness, and paresthesias involving his face and extremities. Muscle strength and deep-tendon reflexes are decreased on neurological exam.
What is going on?
Pufferfish–>Tetrodotoxin
Tetrodoxtoxin binds to voltage-gated sodium channels in nerve and cardiac tissue, preventing sodium influx and DEPOLARIZATION.
GM2 ganglioside metabolites accumulated in system.
Cherry red spot in choroid.
Baby
What is the disorder?
Tay-Sacs
Deficiency in B-hexosaminidase A that results int he accumulation of the cell membrane glycolipid GM2 ganglioside within cell lysosomes.
Autosomal recessive
Enzyme deficiency is sphingomyelinase, so you get accumulation of spingomyelin. Is autosomal recessive.
You will see hepatosplenomegaly, red spot in macula, foam cells, progressive neurodegeration.
Neiman-Pick Disease
X-linked recessive disorder causes by a deficiency in alpha-galactosidase.
Physical signs and symptoms include angiokeratomas, cardiac and renal involvement and pain neuropathy.
Fabry disease
Macrophages that look like crumbled paper, hepatosplenomegaly, pancytopenia, severe bone and joint pain.
What is the disease and what is the deficient enzyme?
Gaucher disease (the macrophages are called gaucher cells).
B-glucocerbrosidase
If you see an MRI of an HIV patient’s brain and you see multiple ring-enhancing lesions, along with oral thrush and lymphadenopathy, what is the diagnosis?
Toxoplasmosis.
Blind as a bat, mad as a hatter, red as a beet, hot as a hair, dry as a bone, the bowel and bladder lose their tone, the heart runs alone.
What kind of toxicity does this describe and how would you counteract it?
Atropine (antimuscarinc drug)
To counteract, you need to increase the concentration of ACh in the synaptic cleft. This can be done by a cholinesterase inhibitor. PHYOSTIGMINE counteracts atropine poisoning.
What do deficiency of the complement factors that form the membrane complex (C5b-C9) cause recurrent infections of?
Neisseria species.
Remember, N can cause bacterial meningitis (common in college dorms). Present with high fevers, chills, altered mentaiton, petechial skin rash from Neisseria-induced small vessel vasculitis (especially affecting palms and soles) and ultimately septic shock
TREATMENT: Ceftriaxone for at least 2 weeks.
Absence of what would cause recurrent viral and fungal infections?
T-cells.
Remember DiGeorge–>T-cell dysfunction due to lack of thymus (3rd and 4th pharyngeal arch did not form properly). Also no parathyroid glands and facial abnormalities with DiGeorge)
These people suffer current infections with catalase-positive organisms (like staph)
Chronic granulomatous disease (X-linked and results from inability of phagocytes to nynthesize NADPH oxidase, which is neceesary of the lysosomal oxidative burst).
N. meinigitidis has pili. What are these used for?
Epithelial attachment of the bacteria to the nasopharynx.
Trigeminal nerve questions:
- Where does CNV2 (maxillary nerve) exit the skull?
- Where does CNV3 (mandibular nerve) exit the skull?
- V2: Foramen rotundum
- V3: Foramen ovale (V3 innervates the muscle of mastication–>massester, medial and lateral pterygoids, and temporalis muscles).
If you have a patient who shows classical signs of meningitis (fever, headache, photophobia, and painful extraocular movements), but the CSF has viral RNA, what can you assume?
90% of viral menigitis cases are from enterovirus infection, so they will get the infection via the fecal-oral route.
Note: Enteroviruses are coxsackieviruses, echoviruses, and polioviruses. Note: poliovirus can cause LMN injury in addition to meningitis, especially in non-immunized individuals from endemic regions.
A 24-year old male is evaluated for chronic headaches and visual changes. An intracranial calcified mass in detected on MRI. The mass is surgically removed. Gross inspection shows cystic spaces filled iwth thick brownish fluid that is rich in cholesterol. The mass most likely shares a common origin with which of the following?
Craniopharyngiomas-calcified cystic tumors
Arise from remnants of rathke’s pouch, which is the embryonic precursor of the anterior pituitary. The commonly cause headaches, growth failure and bitemporal hemianopia.
You are inspecting a swimmer’s ear for external ear infection. While inspecting, you insert a speculum into the external auditory meatus in close contact with its posterior wall. The patient faints during the procedure. What the hell happened?
Vasovagal syncope: stimulated vagal nerve and parasympathetic outflow via the nerve (CN X) leads to decreased HR and blood pressure.
Note: The rest of the external auditory canal (including the external portion of the TM) is innervated by V3 (mandibular). The inner surface of the TM is innervated via glossopharyngeal nerve (CN IX) via its tympanic branch.
What carries afferent taste fibers tot he anterior 2/3 of the tongue as well as efferent parasympathetic preganglionic fibers that will ultimately innervate submandibular and sublingual salivary glands?
Facial Nerve (VII).
Mousy body odor and fair skin = PKU
What amino acid becomes essential in this case?
tyrosine.
PKU patients can not synthesize tyrosine from phenylalanine.
Patient has acidosis and a high methylamalonic acid level. The enzyme that converts methylmalonc acid is not working, thus not converting it to succinyl coA so that it can enter the TCA cycle.
What does the enzyme do?
Methylmalonyl CoA is an isomer of Succinyl CoA, so the enzyme isomerizes the molecule.
Bilateral hemorrhagic destruction of both adrenals can be caused by?
N. Meningitis (can present with DIC and destruction of both adrenals)–>Waterhouse-Friderichsen syndome.)
Claw hand deformity:
Ape hand deformity:
Wrist drop:
Claw hand: Ulnar nerve (and anesthesia over medial 1.5 digits).
Ape hand: Median nerve
Wrist drop: Radial nerve
Beta-endorphin (an endogenous opioid peptide) is derived from proopiomelanocortin (POMC). This molecule is also an enzyme is also a precursor for what molecules?
ACTH and MSH:
The fact that beta-endorphin and ACTH are derived from the same precursor suggest htat there may be a close physiological relationship between the stress axis and the opoid system.
A baby who has hydrocephaly will present with irritability, poor feeding, increased head circumference and enlarged ventricles on CT. What do you see long-term, hypotonicity or hypertonicity of the muscles?
Hypertonicity-because there is upper motor neuron damage that results from stretching of the periventricular pyramidal tracts.
What the first line of treatment for the following type of seizure:
Brief arrhythmic jerking movements that last
Valproic acid is used to treat myoclonic seizures.
First line drugs for the following type of seizure:
Generalized tonic extension of the extremitites, followed by clonic rhythmic movements; loss of consciousness and prolonged postictal confusion.
Tonic-clonic seizure:
Treated with:
- Phenytoin
- Carbamazepine
- Valproate
First line treatment for both of these types of seizures:
- One body part is involved; no loss of consciousness and no post-ictal state are present.
- Almost always temporal lobe (mood changes, illusions, hallucinations); imparied consciouness and postictal state present.
These are:
- Simple partial
- Complex partial
Both treated with carbamazepine.
Note: Aplastic anemia is a dreaded (but rare) side effect.
How do you treat the following type of seizures?
Brief episodes of staring, but no postictal confusion?
Absence seizure
1st line: treat with ethosuximde
2nd line: treat with valproate (if person has absence along with tonic-clonic or myoclonic, treat with valproate.)
A 3-year-old male is hospitalized with prgressive spastic paresis of his lower extremities and choreoathetoid movements. Comprehensive laboratory testing reveals very high arginine levels in both the child’s plasma and the CSF. THe enzyme deficient in this patient is normally involved in the production of what?
Urea: Patient has arginase deficiency.
Arginase in an enzyme in the urea cycle that produces urea and ornitine from arginine. This deficiency is underdiagnosed because it looks like cerebral palsy.
If a patient has a major surgical procedure and then has an increase bp, increased HR, and fever and muscle rigidity after the surgery (along with skin mottling), what do you need to do for that patient to improve his condition?
Give him a drug that will inhibit intracellular calcium release in skeletal muscles. (DANTROLENE)
Malignant hyperthemia is syndrome that occurs due to hypersensitivity of skeletal muscles due to inhalation of anethetics (like halothane) and muscle relaxant succinylcholine. (It is an autosomal dominant trait causing a defect of ryanodine receptors on the surface of the sarcoplasmic reticulum, which is a calcium channel, causing the receptor to release A LOT of calcium).
How do the drugs physostigmine, neostigmine, myridostigmine and edrophonium used to treat myasthenia gravis?
Inhibit acetylcholinesterase degradation in the cholinergic synapses.
What is the mechanism of action for the following drugs:
Atrophine, scopolamine, ipratropium
Cholinergic antagonists that bind to receptors to prevent their interaction with acetylcholine.
How do you treat pheochromacytoma?
alpha-adrenergic antagonists (phentolamine and phenoxybenzamine) which inhibit alpha-receptor mediated sympathetic activity.
Jaw pain that starts in the middle of a meal is characteristic for temporal arteritis. What should you do if temporal arteritis is suspected?
Get ESR–>it is uniformly elevated in patients with temporal arteritis. Then do biopsy. If confirmed, start corticosteroids immediately to prevent possible vision loss.
What is the drug primidone (antiepileptic drug) metabolized to?
Phenobarbital and phenylethymalanoamide. (All three are active anticonvulsants)
What would causes bilateral wedge-shaped bands of necrosis over the cererbral convexity, a few centimeters lateral to the interhemistpheric tissue?
Global cerebral ischemia.
These watershed area are at risk during hypoxemia of the brain.
Cystic tumor in the cerebellum.
Well differentiated neoplasm comprised of SPINDLE CELLS with HAIR-LIKE GLIAL PROCESSES, associated with microcysts. These cells are mixed with rosenthal fibers and granular eosinophilic bodies. Waht type of lesion is it?
Pilocytic astrocytoma.
Note: A cystic tumor of the cerebellum of a child is most likely pilocytic astrocytoma.
Ragged red muscle fibers are seen in what type of disease?
Mitochondrial.
Remember, only women pass on the mitochondria, so if a guy has the disease, there is a 0% chance he will pass to his offspring.
First line treatment for both of these types of seizures:
- One body part is involved; no loss of consciousness and no post-ictal state are present.
- Almost always temporal lobe (mood changes, illusions, hallucinations); imparied consciouness and postictal state present.
These are:
- Simple partial
- Complex partial
Both treated with carbamazepine.
Note: Aplastic anemia is a dreaded (but rare) side effect.
How do you treat the following type of seizures?
Brief episodes of staring, but no postictal confusion?
Absence seizure
1st line: treat with ethosuximde
2nd line: treat with valproate (if person has absence along with tonic-clonic or myoclonic, treat with valproate.)
A 3-year-old male is hospitalized with prgressive spastic paresis of his lower extremities and choreoathetoid movements. Comprehensive laboratory testing reveals very high arginine levels in both the child’s plasma and the CSF. THe enzyme deficient in this patient is normally involved in the production of what?
Urea: Patient has arginase deficiency.
Arginase in an enzyme in the urea cycle that produces urea and ornitine from arginine. This deficiency is underdiagnosed because it looks like cerebral palsy.
If a patient has a major surgical procedure and then has an increase bp, increased HR, and fever and muscle rigidity after the surgery (along with skin mottling), what do you need to do for that patient to improve his condition?
Give him a drug that will inhibit intracellular calcium release in skeletal muscles. (DANTROLENE)
Malignant hyperthemia is syndrome that occurs due to hypersensitivity of skeletal muscles due to inhalation of anethetics (like halothane) and muscle relaxant succinylcholine. (It is an autosomal dominant trait causing a defect of ryanodine receptors on the surface of the sarcoplasmic reticulum, which is a calcium channel, causing the receptor to release A LOT of calcium).
How do the drugs physostigmine, neostigmine, myridostigmine and edrophonium used to treat myasthenia gravis?
Inhibit acetylcholinesterase degradation in the cholinergic synapses.
Claw hand deformity:
Ape hand deformity:
Wrist drop:
Claw hand: Ulnar nerve (and anesthesia over medial 1.5 digits).
Ape hand: Median nerve
Wrist drop: Radial nerve
Beta-endorphin (an endogenous opioid peptide) is derived from proopiomelanocortin (POMC). This molecule is also an enzyme is also a precursor for what molecules?
ACTH and MSH:
The fact that beta-endorphin and ACTH are derived from the same precursor suggest htat there may be a close physiological relationship between the stress axis and the opoid system.
A baby who has hydrocephaly will present with irritability, poor feeding, increased head circumference and enlarged ventricles on CT. What do you see long-term, hypotonicity or hypertonicity of the muscles?
Hypertonicity-because there is upper motor neuron damage that results from stretching of the periventricular pyramidal tracts.
What the first line of treatment for the following type of seizure:
Brief arrhythmic jerking movements that last
Valproic acid is used to treat myoclonic seizures.
First line drugs for the following type of seizure:
Generalized tonic extension of the extremitites, followed by clonic rhythmic movements; loss of consciousness and prolonged postictal confusion.
Tonic-clonic seizure:
Treated with:
- Phenytoin
- Carbamazepine
- Valproate
First line treatment for both of these types of seizures:
- One body part is involved; no loss of consciousness and no post-ictal state are present.
- Almost always temporal lobe (mood changes, illusions, hallucinations); imparied consciouness and postictal state present.
These are:
- Simple partial
- Complex partial
Both treated with carbamazepine.
Note: Aplastic anemia is a dreaded (but rare) side effect.
How do you treat the following type of seizures?
Brief episodes of staring, but no postictal confusion?
Absence seizure
1st line: treat with ethosuximde
2nd line: treat with valproate (if person has absence along with tonic-clonic or myoclonic, treat with valproate.)
A 3-year-old male is hospitalized with prgressive spastic paresis of his lower extremities and choreoathetoid movements. Comprehensive laboratory testing reveals very high arginine levels in both the child’s plasma and the CSF. THe enzyme deficient in this patient is normally involved in the production of what?
Urea: Patient has arginase deficiency.
Arginase in an enzyme in the urea cycle that produces urea and ornitine from arginine. This deficiency is underdiagnosed because it looks like cerebral palsy.
If a patient has a major surgical procedure and then has an increase bp, increased HR, and fever and muscle rigidity after the surgery (along with skin mottling), what do you need to do for that patient to improve his condition?
Give him a drug that will inhibit intracellular calcium release in skeletal muscles. (DANTROLENE)
Malignant hyperthemia is syndrome that occurs due to hypersensitivity of skeletal muscles due to inhalation of anethetics (like halothane) and muscle relaxant succinylcholine. (It is an autosomal dominant trait causing a defect of ryanodine receptors on the surface of the sarcoplasmic reticulum, which is a calcium channel, causing the receptor to release A LOT of calcium).
How do the drugs physostigmine, neostigmine, myridostigmine and edrophonium used to treat myasthenia gravis?
Inhibit acetylcholinesterase degradation in the cholinergic synapses.
Claw hand deformity:
Ape hand deformity:
Wrist drop:
Claw hand: Ulnar nerve (and anesthesia over medial 1.5 digits).
Ape hand: Median nerve
Wrist drop: Radial nerve
Beta-endorphin (an endogenous opioid peptide) is derived from proopiomelanocortin (POMC). This molecule is also an enzyme is also a precursor for what molecules?
ACTH and MSH:
The fact that beta-endorphin and ACTH are derived from the same precursor suggest htat there may be a close physiological relationship between the stress axis and the opoid system.
A baby who has hydrocephaly will present with irritability, poor feeding, increased head circumference and enlarged ventricles on CT. What do you see long-term, hypotonicity or hypertonicity of the muscles?
Hypertonicity-because there is upper motor neuron damage that results from stretching of the periventricular pyramidal tracts.
What the first line of treatment for the following type of seizure:
Brief arrhythmic jerking movements that last
Valproic acid is used to treat myoclonic seizures.
First line drugs for the following type of seizure:
Generalized tonic extension of the extremitites, followed by clonic rhythmic movements; loss of consciousness and prolonged postictal confusion.
Tonic-clonic seizure:
Treated with:
- Phenytoin
- Carbamazepine
- Valproate
First line treatment for both of these types of seizures:
- One body part is involved; no loss of consciousness and no post-ictal state are present.
- Almost always temporal lobe (mood changes, illusions, hallucinations); imparied consciouness and postictal state present.
These are:
- Simple partial
- Complex partial
Both treated with carbamazepine.
Note: Aplastic anemia is a dreaded (but rare) side effect.
How do you treat the following type of seizures?
Brief episodes of staring, but no postictal confusion?
Absence seizure
1st line: treat with ethosuximde
2nd line: treat with valproate (if person has absence along with tonic-clonic or myoclonic, treat with valproate.)
A 3-year-old male is hospitalized with prgressive spastic paresis of his lower extremities and choreoathetoid movements. Comprehensive laboratory testing reveals very high arginine levels in both the child’s plasma and the CSF. THe enzyme deficient in this patient is normally involved in the production of what?
Urea: Patient has arginase deficiency.
Arginase in an enzyme in the urea cycle that produces urea and ornitine from arginine. This deficiency is underdiagnosed because it looks like cerebral palsy.
If a patient has a major surgical procedure and then has an increase bp, increased HR, and fever and muscle rigidity after the surgery (along with skin mottling), what do you need to do for that patient to improve his condition?
Give him a drug that will inhibit intracellular calcium release in skeletal muscles. (DANTROLENE)
Malignant hyperthemia is syndrome that occurs due to hypersensitivity of skeletal muscles due to inhalation of anethetics (like halothane) and muscle relaxant succinylcholine. (It is an autosomal dominant trait causing a defect of ryanodine receptors on the surface of the sarcoplasmic reticulum, which is a calcium channel, causing the receptor to release A LOT of calcium).
How do the drugs physostigmine, neostigmine, myridostigmine and edrophonium used to treat myasthenia gravis?
Inhibit acetylcholinesterase degradation in the cholinergic synapses.
How do you treat pheochromacytoma?
alpha-adrenergic antagonists (phentolamine and phenoxybenzamine) which inhibit alpha-receptor mediated sympathetic activity.
Jaw pain that starts in the middle of a meal is characteristic for temporal arteritis. What should you do if temporal arteritis is suspected?
Get ESR–>it is uniformly elevated in patients with temporal arteritis. Then do biopsy. If confirmed, start corticosteroids immediately to prevent possible vision loss.
What is the drug primidone (antiepileptic drug) metabolized to?
Phenobarbital and phenylethymalanoamide. (All three are active anticonvulsants)
What would causes bilateral wedge-shaped bands of necrosis over the cererbral convexity, a few centimeters lateral to the interhemistpheric tissue?
Global cerebral ischemia.
These watershed area are at risk during hypoxemia of the brain.
Cystic tumor in the cerebellum.
Well differentiated neoplasm comprised of SPINDLE CELLS with HAIR-LIKE GLIAL PROCESSES, associated with microcysts. These cells are mixed with rosenthal fibers and granular eosinophilic bodies. Waht type of lesion is it?
Pilocytic astrocytoma.
Note: A cystic tumor of the cerebellum of a child is most likely pilocytic astrocytoma.
Ragged red muscle fibers are seen in what type of disease?
Mitochondrial.
Remember, only women pass on the mitochondria, so if a guy has the disease, there is a 0% chance he will pass to his offspring.
