User:Yanping Nora Soong/M1/Exam 6

=Diagnostic radiology=

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See: Chest radiograph
 * PA (posterior => anterior): typically performed on ambulatory adults
 * Least amount of magnification (and scattering) for the heart


 * AP (anterior => posterior) typically performed on pediatric patients OR patients who are weak, unresponsive, very sick, bed-confined, etc.
 * X-ray beam is scattered by the heart closer to the source and further away from the detector (enlarged cardiac silhouette)

Systematic approach: ABCDs

 * Airway: Trachea, mediastinal width, aortic knob (do not miss: tracheal deviation)
 * Breathing: Lung field outlines, (a)symmetry, pleural space (do not miss: pneumothorax)
 * Circulation: Heart size on PA film, heart borders, heart shape
 * Diaphragm: Hemidiaphragm levels, costophrenic angles, diaphragm contour lines (do not miss pneumoperitoneum)


 * RIPE: Rotation, Inspiration, Picture, Exposure
 * Soft tissues / skeleton: Breast tissue, calcification, bones

Birth defects

 * Tetralogy of Fallot due to pulmonary atresia with ventricular septal defect
 * Double aortic arch / vascular ring

Abdomen

 * Pancreatic cancer (90% of cases are pancreatic adenocarcinoma)
 * Pt is often asymptomatic. Signs and symptoms show up late in the disease process:
 * Courvoisier's law (" a painless palpably enlarged gallbladder accompanied with mild jaundice is unlikely to be caused by gallstones")
 * Epigastric pain radiating to the back
 * Painless obstructive jaundice
 * recent onset of type 2 diabetes
 * Dilatation of pancreatic duct and intrahepatic biliary ducts (due to compressive obstruction / mass effect)
 * Pruritus (from bile salts entering the bloodstream causing elevated serum bilirubin)
 * Radiologic markers of Whipple procedure / Pancreaticoduodenectomy

=Pathology and histology=

Cell death type (high yield)

 * Apoptosis
 * Coagulative necrosis most common
 * Liquefactive necrosis second most common/significant (on exams)

Endocrine

 * Adrenal crisis and adrenal cortical atrophy due to withdrawal from exogenous glucocorticoids (e.g. lecture case due to stomach virus / vomiting causing unintentional drug withdrawal)
 * Gross pathology: Cortex in case is much thinner than medulla cf. normal/healthy adrenal gland
 * Histology: Cells in the zona fasciculata lack lipid droplets, empty voids due to shrinking of cell volumes

Liver

 * Mallory hyaline (Mallory body) associated with alcoholic liver disease
 * Histology of paracetamol poisoning: coagulative necrosis around zone 3 of the liver acinus (liver lobule) around central venule
 * Remember to review and add Case 3, Slide 35 (Introduction to Pathology - Part 2 (Interactive Workshop) / Cellular Alterations and Circulation - Clinico-Pathological Correlation, Dr. Lto, Friday Nov 17), to class Anki deck for this lecture ; H&E slide taken from Robbins Pathology of Disease
 * Features of well-developed coagulative necrosis visible on pathologic specimens around 24 hour hours of death of cells
 * Architecture of tissue is retained (initially), cytoplasm is hypereosinophilic, cells are anucleate
 * Biochemistry: CYP3A4 and CYP2E1 metabolism of paracetamol to NAPQI (oxidant), antidote is N-acetylcysteine


 * Distinguish perisinusoidal space v. liver sinusoid on histology slides

=Biochemistry=

Lipid transport

 * PCSK9 - LDL transporter recycling

Vitamins and cofactors

 * Ascorbic acid (impact of deficiency => scurvy and bone defects)
 * Collagen biosynthesis
 * prolyl hydroxylase
 * lysyl hydroxylase (clarify ascorbic acid's role in lysyl oxidase)
 * Norepinephrine biosynthesis via dopamine beta-hydroxylase
 * Tyrosine catabolism (hydroxylation of Homogentisic acid)
 * Carnitine biosynthesis via lysyl hydroxylase


 * Post-translational modification of specific peptide hormones (hydroxylation of C-terminal glycine to amide terminus)
 * Iron absorption (reduction of poorly-soluble ferric ion to better-soluble ferrous ion)
 * (cf. anemia due to hepcidin)


 * Stabilizes tetrahydrobiopterin in its reduced form
 * Stimulates osteoblast activity over osteoclast activity
 * Tetrahydrobiopterin
 * Thiamine (B1) (deficiency => beriberi)
 * Carried into the mitochondria via Mitochondrial thiamine pyrophosphate carrier (SLC25A19)
 * Required for pyruvate dehydrogenase activity to form acetyl CoA
 * Impaired biosynthesis of acetylcholine (from choline and acetyl-CoA)


 * "What metabolites in serum and urine can be used to differentiate between a folate deficiency and a vitamin B12 deficiency? What information is revealed by the Schilling test and modified Schilling test?"

Pathogen-associated molecular patterns

 * Lipopolysaccharide (LPS) on gram-negative bacteria

Clusters of differentiation (diagnostic / immunohistological)

 * CD3: T-cell co-receptor for the T-cell receptor (TCR), ubiquitously expressed by pro-thymocyte precursors to all T-cells, and differentiated T-cells. Required for T-cell activation
 * Section CD3 (immunology): "The pro-thymocytes differentiate into common thymocytes, and then into medullary thymocytes, and it is at this latter stage that CD3 antigen begins to migrate to the cell membrane. The antigen is found bound to the membranes of all mature T-cells, and in virtually no other cell type... The antigen remains present in almost all T-cell lymphomas and leukaemias, and can therefore be used to distinguish them from superficially similar B-cell and myeloid neoplasms."


 * CD4: TCR co-receptor, required for activation of helper T-cells, specific for MHC Class II antigens
 * CD8: TCR co-receptor, required for activation of cytotoxic T-cells, specific for MHC Class I antigens, also found on dendritic cells and natural killer (NK) cells.
 * CD14: Coreceptor expressed by all macrophages, binds to LPS
 * CD15: Important for leukocyte tethering and rolling. Constitutively expressed by all granulocytes, but not in unactivated (resting) lymphocytes
 * CD19 (B-Lymphocyte Surface Antigen B4): present on all B cells
 * CD34: ubiquitous (but not exclusive to) marrow-bound hematopoietic stem cells
 * CD45 (single-pass membrane protein expressed by all differentiated hematopoetic cells (except erythrocytes and some plasma B cells)


 * T regulatory cells (which suppress immune response) express FOXP3, CD3, CD4, CD25 and secrete IL-10 which suppresses immune response
 * V(D)J recombination: pro-B cells will express CD19 and CD20

Stimulatory

 * Tumor necrosis factor (TNF-α)
 * Interleukin-1
 * IL-1β


 * IL-8
 * IL-12
 * CD27 (member of tumor necrosis factor receptor superfamily; co-stimulatory immune checkpoint)
 * Required for long-term maintenance of cell-mediated immunity

Regulatory / inhibitory

 * IL-10

Cancer markers

 * Mismatch repair endonuclease PMS2

Plasma membrane transporters

 * ATP-binding cassette transporter (ABCs)
 * Solute carrier proteins (SLCs)

Mitochrondrial membrane transporters

 * Malate-aspartate shuttle
 * Glycerol-3-phosphate shuttle

Nuclear membrane transporters
=Infectious disease and epidemiology / clinical microbiology=

Epidemiology

 * Prevalence v. incidence
 * Net reproduction rate (R0)

Virulence factors

 * Bacterial capsule
 * Bacterial toxins
 * Bacterial adhesin
 * Invasin
 * Pathogenicity island

Viral
=To be organized=


 * Protein phosphatase 1
 * Glycogen synthase
 * Glycogen phosphorylase

=Inline citations=