FMR 2024 Flashcards
Teaching
Autophagy
First, intracellular organelles and portions of cytosol are sequestered in an ER-derived phagophore.
Phagophore matures into an autophagic vacuole, autophagosome.
An autophagosome combines with a lysosome to form an autophagolysosome.
three main types of cells in the body
labile, stable, and permanent
Labile cells
These cells divide continuously to replace lost cells. They are constantly moving through the cell cycle and never enter the G0 phase. Examples include epithelial cells, hematopoietic stem cells, and keratinocytes.
Stable cells
These cells have a long lifespan and divide slowly, but can divide rapidly when needed. They usually stay in the G0 phase of the cell cycle, but can enter G1 and divide if stimulated. Examples include parenchymal cells of the liver and kidney, hepatocytes, and renal tubular epithelial cells.
Permanent cells
These cells never divide and cannot replicate, even when stressed or if other cells die. They remain in the G0 phase of the cell cycle and are unable to regenerate. Examples include neurons, cardiac myocytes, and skeletal muscles.
three types of muscle fibres
Type 1: Slow oxidative (SO) fibers contract relatively slowly and use aerobic respiration (oxygen and glucose) to produce ATP. They produce low power contractions over long periods and are slow to fatigue.
Type 2 A: Fast oxidative (FO) fibers have fast contractions and primarily use aerobic respiration, but because they may switch to anaerobic respiration (glycolysis), can fatigue more quickly than SO fibers.
Type 2 B: Fast glycolytic (FG) fibers have fast contractions and primarily use anaerobic glycolysis. The FG fibers fatigue more quickly than the others[3].
Hemoptysis vs pseudohemoptysis
Hemoptysis must be differentiated from pseudohemoptysis, which is blood that originates from nasopharyngeal or gastrointestinal sources.
Hemoptysis
the expectoration of blood from the lower respiratory tract, usually from bronchial arteries. The most common causes are acute respiratory infections, cancer, bronchiectasis, and chronic obstructive pulmonary disease. No cause is identified in 20% to 50% of cases.
Causes of hemoptysis.
Worldwide, tuberculosis is the most common cause of hemoptysis. In ambulatory settings of countries without limited resources, hemoptysis is often caused by acute respiratory infections, chronic obstructive pulmonary disease, cancer, and bronchiectasis. However, 20% to 50% of cases are cryptogenic, with no cause found on computed tomography (CT) or bronchoscopy
Normal heart weight male and female
250 - 300 g female
300 to 350 g male
Cardiomegaly weight
Cardiomegaly is defined as a heart with a weight at autopsy that exceeds the 95th percentile of the reference population. Autopsy indicates that cardiomegaly is present if the heart weighs more than >399 grams in women and >449 grams in men.
Familial hypertrophic cardiomyopathy is inherited how?
Usually autosomal dominant.
Adjuvants
Adjuvants increase the efficiency or response of a factor or treatment. Adjuvant treatment is applied after initial treatment for cancer, especially to suppress secondary tumor formation.
Nitric oxide
A gas that your body makes naturally. It helps relax your blood vessels, so it may help reduce blood pressure, improve athletic performance and enhance sexual functioning in men with erectile dysfunction.
Nitric oxide
Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula NO. It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its chemical formula (*N=O. or *NO).
Nitrous oxide (N2O)
laughing gas.
nitro in car racing
The chemical formula for nitromethane, also known as “nitro”, is CH3NO2.
Diagnosis of systemic sclerosis
Diagnosis is by clinical suspicion, presence of autoantibodies (specifically anticentromere and anti-scl70/antitopoisomerase antibodies), and occasionally by biopsy. Of the antibodies, 90% have a detectable antinuclear antibody. Anticentromere antibody is more common in the limited form (80–90%) than in the diffuse form (10%), and anti-scl70 is more common in the diffuse form.
most common treatment for calcinosis cutis.
While all options are used to treat calcinosis cutis, diltiazem is the most commonly used. It decreases the amount of calcium that enters cells and macrophages of the damaged tissues. High doses at 2 mg/kg/d to 4 mg/kg/d are necessary for therapeutic response.
Calcinosis cutis
Calcinosis cutis is a condition in which calcium salts are deposited in the skin and subcutaneous tissue. It is classified into five main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis.
calciphylaxis.
a rare but devastating disorder most commonly observed in patients with end-stage renal disease, although it does occasionally develop in patients with acute renal failure, normal renal function, or earlier stages of chronic kidney disease (non-uremic calciphylaxis). Also known as calcific uremic arteriolopathy, it is characterized by painful skin lesions caused by cutaneous arteriolar calcification leading to tissue ischemia and infarction. Calciphylaxis is associated with substantial morbidity due to severe pain, nonhealing wounds, and frequent hospitalizations. It is a highly fatal condition with 1-year mortality rates greater than 50%, most often due to sepsis.
most commonly used medication for calcinosis cutis
Diltiazem reduces the amount of calcium that enters the cells and macrophages at the sites of damage.
High dosing at 2 to 4 mg/kg/d is needed for good response.
Diltiazem is a calcium channel blocker.
Glia
Glia are cells that support the neurons. They include the following:
Astrocytes: star-shaped glial cells that supply nutrients to the neurons, act as nerve detoxifiers and electrical insulators, protect from harmful macromolecules, and contribute to CNS repair and scar formation.
Oligodendrocytes: myelinate the CNS axons.
Ependymal cells: line the ventricles and control CSF production and flow.
Microglia: comprise the CNS’ macrophage system.
most sensitive and specific antemortem diagnostic test for the evaluation of suspected CJD
The most sensitive and specific antemortem diagnostic test is the RT-QuIC technique. It should be the initial test in the evaluation of suspected CJD.
test for prion disease
CSF 14-3-3 protein.
An elevated tau level (greater than 1150 picogram/mL) has more accuracy and specificity than 14-3-3 protein as a diagnostic test for CJD, although both tests can produce significant false-negative and false-positive results.
Huntington’s disease classically presents with
cognitive decline, with emotional lability and clumsiness. Features on an MRI would indicate frontal lobe atrophy and enlargement of the frontal horns of the lateral ventricles
Atypical lipomatous tumor shows what chromosome abnormality?
Atypical lipomatous tumor shows a chromosome 12 duplication (12q15).
This chromosomal aberration corresponds to an amplification of the MDM2 gene.
Lung adenocarcinoma is associated with what extrapulmonary features?
hypertrophic osteoarthropathy, which manifests as clubbing, periostitis of long bones, and arthritis.
Tay-Sachs disease
GM2 ganglioside waste product builds up in nerve cells.
enzyme hexosaminidase A (HEX A).
chromosome 15 genetic disorders
Nucleosome
the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins[1] and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin.
improper closure of the neural tube
results in birth defects, which include the opening of the cranium or spine. Examples – Spina bifida, Encephalocele, Anencephaly, etc.
neurocristopathies.
The abnormal migration, death or differentiation of neural crest cells during embryonic development, results in a condition called neurocristopathies.
The closure of the neural tube usually happens by the
4th week of pregnancy. If the neural tube is not closed properly, it results in birth defects which include the opening of the cranium or spine. Examples – Spina bifida, Encephalocele, Anencephaly, etc.
Names of the neuron cell body
Soma/perikaryon
Satellite glial cells
formerly called amphicytes, are glial cells that cover the surface of neuron cell bodies in ganglia of the peripheral nervous system. Thus, they are found in sensory, sympathetic, and parasympathetic ganglia.
Satellite glial cells
Nerves
Avon bundle in the peripheral nervous system.
NO nerves exist inside the brain or spinal cord.
So “peripheral nerves” is a redundant term.
the structure of a rope-like tail of fibers at the caudal end of the spinal cord
cauda equina
Phlegmon
a localized area of acute inflammation of the soft tissues. It is a descriptive term which may be used for inflammation related to a bacterial infection or non-infectious causes (e.g. pancreatitis). Most commonly, it is used in contradistinction to a “walled-off” pus-filled collection (abscess), although a phlegmon may progress to an abscess if untreated. A phlegmon can localize anywhere in the body. The Latin term phlegmōn is from Ancient Greek φλέγω (phlégō) ‘burn’.
two most consistent morphologic correlates of reversible cell injury
cellular swelling and fatty change.
Chilblains
also known as pernio, is a medical condition in which damage occurs to capillary beds in the skin, most often in the hands or feet, when blood perfuses into the nearby tissue, resulting in redness, itching, inflammation, and possibly blisters.[2]
It occurs most frequently when predisposed individuals, predominantly women,[3] are exposed to cold and humidity. Ulcerated chilblains are referred to as kibes.
the most common genetic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) with a prevalence of 1 in 500 in the general population. The first pathological case series at post mortem in 1957. First described by Vulpian, as “idiopathic hypertrophic subaortic stenosis” in 1868,
most common cause of sudden cardiac death in young people
Hypertrophic cardiomyopathy (HCM)
What is the outcome for cutaneous viral warts?
In children, even without treatment, 50% of warts disappear within six months, and 90% are gone in 2 years.
Viral warts are more persistent
in adults, but they clear up eventually. They are likely to recur in patients that are immunosuppressed, for example, organ transplant recipients. Recurrence is more frequent in tobacco smokers.
Alternobaric facial paresis
neurapraxia of the seventh cranial nerve due to pressure effects. The pressure in the middle ear can cause compression of the facial (seventh cranial) nerve with symptoms that are similar to Bell’s palsy. It occurs on the ascent with diving.
Examination shows unilateral facial paralysis, sometimes accompanied by altered taste sensation. The otoscopic examination may find a bulge of the tympanum. Equalization of the middle ear pressure can make it disappear. Simple maneuvers should be tried to reduce pressure in the eardrum. Yawning and swallowing may open the Eustachian tube.
Misdiagnosis, as neurologic decompression sickness (DCS) or air embolism, results in unnecessary recompression treatment and restriction of diving.
the most common peripheral paralysis of the seventh cranial nerve
Bell palsy
most common cause of bilateral acute nontraumatic facial palsy
Lyme disease
Inborn Errors of Metabolism
a heterogeneous group of disorders that may be inherited or may occur as the result of spontaneous mutation. These diseases involve failure of the metabolic pathways involved in either the break-down or storage of carbohydrates, fatty acids, and proteins. 1 in 2500 births
least common form of nephrolithiasis
Cystine stones
most common type of nephrolithiasis
Calcium oxalate stones
Alkaptonuria
a rare autosomal recessive genetic disorder resulting from a deficiency of homogentisate 1,2- dioxygenase (HGD). The HGD gene is expressed in the liver, kidney, prostate, small intestine, and colon. This enzyme plays a role in the metabolism of tyrosine that converts homogentisic acid into malate and acetoacetate. In the absence of HGD, homogentisic acid produced in excess by the liver oxidizes into an ochronotic pigment polymer.
Maple syrup urine disease
The enzyme deficient in this patient is branched-chain alpha-keto acid dehydrogenase, which breaks down branched-chain amino acids like leucine, isoleucine, and valine.
Tay-Sachs disease (TSD),
autosomal recessive, lethal neurodegenerative disorder.
deficiency of the enzyme hexosaminidase-A, resulting in the accumulation of GM2 gangliosides. Tay-Sachs disease involves mutations in the gene HEXA, located at 15q23, which encodes β-hexosaminidase-A.
A cherry-red spot in the retina is a near-pathognomonic finding in TSD. infantile TSD usually die by age 4 to 5 years.
In late-onset disease, there are progressive gait difficulties and motor impairments, which often require the use of adaptive equipment and mobility assistance. Psychiatric symptoms may be resistant to treatment. Progressive neurologic deterioration often leads to a vegetative state, and death usually occurs by 10 to 15 years of age.
Krabbe disease
progressive neurologic condition due to abnormal myelination. It results from a deficiency in the lysosomal enzyme galactocerebrosidase.
Gaucher disease
a lipid storage defect involving an accumulation of glucocerebroside due to a lack of the lysosomal enzyme glucocerebrosidase
phenylketonuria (PKU)
The classic form is caused by a deficiency in phenylalanine hydroxylase, which converts the amino acid phenylalanine to tyrosine. The co-factor involved in this biochemical reaction is tetrahydrobiopterin (BH4). Patients with phenylketonuria have a buildup of phenyl ketones, such as phenylacetate and phenylpyruvate, which can be detected through a urine sample. Blood levels of phenylalanine are also elevated, and all newborns are tested for this as part of routine metabolic screening at birth.
Hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficiency
an X-linked recessive disorder mainly affecting males. HGPRT is an essential enzyme for salvaging or recycling purine bases released from nucleotide degradation.
HGPRT deficiency can present as psychomotor delay, other neurologic manifestations, and the observation of orange crystals in the diapers due to crystalluria.
Lesch-Nyhan syndrome is a severe form of HGPRT deficiency characterized by severe action dystonia, intellectual disability, and self-mutilation.
Glycogen storage disorders that primarily affect the liver include:
Glycogen synthase-2 deficiency (GSD type 0a)
Glucose-6-phosphatase deficiency (GSD type Ia)
Glucose-6-phosphate transporter deficiency (GSD type Ib)
Glycogen debrancher deficiency (GSD type III)
Glycogen branching enzyme deficiency (GSD type IV)
Liver phosphorylase deficiency (GSD type VI)
Phosphorylase kinase deficiency (GSD type IXa)
GLUT2 deficiency or Fanconi-Bickel disease
Glycogen storage disorders that primarily affect the skeletal muscles include:
Muscle phosphorylase deficiency (GSD type V)
Phosphofructokinase deficiency (GSD type VII)
Phosphoglycerate mutase deficiency (GSD type X)
Lactate dehydrogenase A deficiency (GSD type XI)
Aldolase A deficiency (GSD type XII)
Beta-enolase deficiency (GSD type XIII)
Phosphoglucomutase-1 deficiency (GSD type XIV)
Glycogen storage disorders that affect both skeletal and cardiac muscles include:
Lysosomal acid maltase deficiency (GSD type IIa)
Lysosome-associated membrane protein 2 deficiency (GSD type IIb)
Glycogenin-1 deficiency (GSD type XV)
Muscle glycogen synthase deficiency (GSD type 0b)
Neutralizers of free radicals
Superoxide dismutase
Catalase
Glutathione peroxidase
vitamins
superoxide dismutase
catalyzes the dismutation (or partitioning) of the superoxide (O2-; “O”2 minus) anion radical into normal molecular oxygen (O2) and hydrogen peroxide (H2O2).
three major families of superoxide dismutase
Red infarctions (hemorrhagic infarcts)
generally affect the lungs or other loose organs (testis, ovary, small intestines)
Henoch schonlein purpura
IgA Vasculitis.
IgAV is primarily a disease of children, with only 10% of cases occurring in adults older than 18.
Relapse is common in the first 4 to 6 months, but full recovery usually occurs with less than 1% mortality.
IgA vasculitis with nephritis vs IgA nephropathy
IgAV with nephritis is more likely to first occur in children younger than 15 years of age.
IgAV with nephritis is more likely to present with extrarenal symptoms.
IgAV with nephritis has a 98% clinical remission.
IgA nephropathy progress to end-stage renal disease within 20 years of diagnosis in 30% to 50% of cases.
IgAV with nephritis presents more often during the winter “cold” season.
IgA nephropathy does not show seasonality.
the most common glomerulonephritis in the world.
IgA nephropathy
IgA Vasculitis.
IgAV is primarily a disease of children, with only 10% of cases occurring in adults older than 18.
Relapse is common in the first 4 to 6 months, but full recovery usually occurs with less than 1% mortality.
The presentation can be similar to IgA nephropathy but with more skin, GI, and joint manifestations and fewer chronic effects.
Histology shows more IgA deposits in the capillaries and subendothelial space and more likely co-presence of IgG than Iga nephropathy.
Galactose-deficient-IgA1 is commonly found in IgAV, especially with renal involvement.
The diagnosis of Henoch-Schönlein purpura
based on the presence of petechiae (without thrombocytopenia) or palpable purpura that predominantly affects the lower limbs plus at least 1 of the following 4 characteristics: 1. abdominal pain, 2. arthralgia or arthritis, 3. renal involvement (proteinuria, red blood cell casts, or hematuria), 4. proliferative glomerulonephritis or leukocytoclastic vasculitis with predominant deposition of IgA on histology.
Serum IgA levels are non-diagnostic. There are no definitive tests for the diagnosis of Henoch-Schönlein purpura.
Potential life-threatening complications of Henoch-Schönlein purpura (HSP)
intussusception, bowel perforation, bowel gangrene, and massive hemorrhage. Intussusception is the most common life-threatening gastrointestinal complication, affecting 3% to 4% of patients.
Causes of diffuse abdominal pain
Peritonitis
Pancreatitis
Sickle cell crisis
Early appendicitis
Mesenteric thrombosis
Gastroenteritis
Dissecting or ruptured aortic aneurysm
Intestinal obstruction
Diabetes mellites
Inflammatory bowel disease
Irritable bowel
Differential diagnosis of acute pancreatitis includes other causes of epigastric abdominal pain
Peptic ulcer disease (PUD)
Choledocholithiasis
Cholecystitis
Perforated viscus
Acute Mesenteric Ischemia
Intestinal obstruction
Differentials of chronic pancreatitis include
Acute recurrent pancreatitis
Pancreatic malignancy
Chronic mesenteric ischemia
Differentials of chronic pancreatitis include
Acute recurrent pancreatitis
Pancreatic malignancy
Chronic mesenteric ischemia
Differential diagnosis of alcohol acute pancreatitis
Pancreatitis secondary to other causes
Gastritis or gastroenteritis
Biliary disease secondary to obstructive or infectious pathology
Bowel perforation or obstruction
Nephrolithiasis
Ectopic pregnancy
Ischemic heart disease
Pneumonia
Aortic pathology
Form pores in the mitochondrial membrane in intrinsic apoptotic pathway
BAX and BAK of the bel-2 family of proteins.
BAX and BAK (BAd for survival) form pore in the mitochondria allowing release of cytochrome C into the cytoplasm which activates caspases.
Apoptotic three pathway
Intrinsic pathway
Extrinsic pathway
Perforin/granzyme B pathway
Bcl-2 overexpression
follicular lymphoma t[14;18]
Function of bel-2
Binds BAX or BAK to prevent them from forming pore in the mitochondrion. Bcl-2 2 and Bcl-xL are antiapo[totic (Be clever, live).
Another name for the extrinsic apoptotic pathway
death receptor pathway
FasL binding to Fas (CD95) or
TNF-alpha binds to it’s receptor
Autoimmune lymphoproliferative syndrome
Caused by defective Fas-FasL interaction causing failure of clonal deletions causing increased numbers of self-reacting lymphocytes. Presents with lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias.
Caused by defective Fas-FasL interaction
Autoimmune lymphoproliferative syndrome.
Caused by defective Fas-FasL interaction causing failure of clonal deletions causing increased numbers of self-reacting lymphocytes. Presents with lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias.
interferon
WORD ORIGIN
(interference with the growth of the virus)
From 1957 to 1974, several investigating groups reported on the functional aspects of molecules secreted by ‘stimulated’ (sensitized) cells using different biological systems. Isaacs and Lindenmann11 while working with live influenza virus grown in chicken embryo chorioallantoic membranes observed that cells pre-treated with heat-inactivated influenza virus inhibited the growth of live influenza virus. They conjectured that the phenomenon was mediated by a protein released by cells in the chorioallantoic membrane that was pre-treated with heat-inactivated influenza virus. They named it ‘interferon’ (interference with the growth of the virus).
PERFORIN/GRANZYME B APOPTOTIC PATHWAY
Release of granules containing perforin and granzyme B by immune cells (cytotoxic t-cell and natural killer cell). Perforin from a pore for granzyme B to enter the target cell.
Griffith point
Splenic flexure watershed area
Sudeck point
Rectosigmoid junction watershed area
Neurons most vulnerable to hypoxic-ischemic insults
Purkinje cells of the cerebellum and pyramidal cells of the hippocampus and neocortex.
xenobiotics
Most drugs are xenobiotics, ie, chemical substances not naturally produced by the body.
Innate immunity AKA
natural immunity
native immunity
adaptive immunity AKA
acquired immunity
specific immunity
By convention, the term immune response usually refers to adaptive immunity.
By convention, the term immune response usually refers to
adaptive immunity.
acquired immunity
specific immunity
Components of innate immunity
Epithelial barriers
Phagocytic cells (mainly neutrophils and macrophages).
Dendritic cells.
Mast cells.
Natural killer cells and other innate lymphoid cells.
Plasma proteins (complement system, mannose-binding lectin, C-reactive protein).
Lung surfactant.
Pattern recognition receptor ligands
Pathogen-associated molecular patterns.
Damage-associated molecular patterns.
normal pressure Starling forces
artery hydrostatic?
venous hydrostatic?
osmotic?
normal pressure
artery hydrostatic 32 mm Hg
venous hydrostatic 12 mm Hg
osmotic 25 mm Hg
Filopodia
The leukocyte moves by exdending filopodia
The leukocyte moves by exdending
filopodia
Efferocytosis
a physiological process where phagocytic cells remove and digest dying cells, or apoptotic cells (ACs). The term comes from the Latin word efferre, which means “to carry the dead to the grave”.
