Clinical Correlations

Question 1

What are muscular dystrophies?

Answer 1

Genetic conditions that cause progressive weakness and atrophy of skeletal muscles, starting in childhood

Question 2

What is the most common muscular dystrophy and what are its characteristics?

Answer 2

Duchenne muscular dystrophy (DMD)

X-linked recessive mutation of gene encoding dystrophin

Dysfunctional dystrophin leads to uneven transfer of force through sarcolemma to external lamina and endomysium during contraction.

Leads to weaker contractions and damage to sarcolemma and external lamina

Damage to EL also damages satellite cells - tissue less able to repair and regenerate, death of muscle fibers and satellite cells

Question 3

What happens within a few days after minor damage to skeletal muscle repair?

Answer 3

Satellite cells activate, proliferate, and differentiate into myoblasts

Myoblasts align and fuse end to end to form myotubes and myotubes fuse side to side to form muscle fibers

Question 4

What occurs with satellite cells with age or injury?

Answer 4

Number of satellite cells decreases with age - slower healing as age increases

Muscle injury damages external lamina usually damages/kills satellite cells - intact EL is important for muscle cell repair

Question 5

If damage to skeletal muscle fibers is extensive, what occurs?

Answer 5

Fibers not repaired and eventually replaced with scar tissue and fat

Question 6

Why does cardiac muscle tissue not regenerate after cell damage?

Answer 6

No satellite cells

Dead cells replaced with collagenous CT scar tissue

Question 7

What occurs with the tau protein in patients with Alzheimer’s Disease?

Answer 7

Hyperphosphorylation of tau protein causes it to aggregate in an insoluble form

Makes tau protein unable to bind to microtubules - they become unstable and start disintegrating

Unbound tau forms clumps, neurofibrillary tangles, that disrupt cell function and can lead to neuronal death

Question 8

What causes dendritic spines to decrease in number?

Answer 8

Dendritic spines decrease with age and with poor nutrition

Patients with trisomy 21 or trisomy 13 also have fewer dendritic spines

Question 9

What do some viruses use to travel from neuron to neuron in CNS?

Answer 9

Viruses like HSV and rabies use retrograde transport

Also method that toxins are transported from body periphery to CNS

Question 10

What are most primary brain tumors in adults derived from?

Answer 10

Fibrous astrocytes

Question 11

How often does the process of PNS axon regeneration occur?

Answer 11

3-4 mm/day

Question 12

Are tracts in the CNS able to regenerate?

Answer 12

No

Question 13

What is hyperuricemia?

Answer 13

Elevated uric acid

Deposition of sodium urate crystals

Caused by:
Decreased renal clearance of urate - renal insufficiency and metabolic acidosis

Increased urate production - hemolytic disease and chemotherapy

Question 14

What is gout?

Answer 14

Recurrent attack of inflammatory arthritis

Deposition of sodium urate crystals in the joints of the extremities

Triggers an inflammatory response with pain and join swelling

Can progress to acute gouty arthritis

Question 15

What are kidney stones?

Answer 15

Common in patients who suffer gout

Deposition of uric acid stones in the kidney - uric acid urolithiasis

Question 16

What is allopurinol?

Answer 16

Analog of hypoxanthine converted to oxypurinol by xanthine oxidase

Inhibit xanthine oxidase and conversion of hypoxanthine and xanthine to uric acid

Hypoxanthine and xanthine more soluble than uric acid - eliminated in urine

Reduces uric acid formation

Question 17

What is the rare hereditary condition that presents with high levels of orotic acid in the urine and hypochromic megaloblastic anemia?

Answer 17

Orotic aciduria

High levels of orotic acid in urine causes crystalluria

Hypochromic megaloblastic anemia - unresponsive to B12 and folic acid

Growth retardation

Neurologic abnormalities

Question 18

What is severe combine immunodeficiency syndrome (SCID)?

Answer 18

Group of immune disorders impacting both B cell and T cell function

15% of cases due to mutation in adenosine deaminase

Adenine metabolites build up

Accumulation of dATP inhibits ribonucleotide reductase

Conversion of NDPs to corresponding dNDPs blocked

Lack of purine and pyrimidine deoxyribonucleotides block DNA replication

Inability to replicate DNA prevent cell proliferation events required for effective immune response

Alternatively, adenine metabolites directly toxic to lymphocytes

Question 19

What occurs with inhibition of thymidylate synthase?

Answer 19

Blocks de novo dTMP synthesis

Reduced dTTP available for DNA synthesis and blocks cell proliferation

Question 20

What is 5-fluorouracil?

Answer 20

Analog of uracil

Cancer treatment for colon carcinoma

For dermatology uses - topical for actinic keratosis

Question 21

What is methotrexate?

Answer 21

Folate analog

Used in treatment of various cancers, severe psoriasis, and sever rheumatoid arthritis

Inhibits dihydrofolate reductase

Lack of N5N10-methylene THF inhibits thymidylate synthase

Lack of pyrimidine synthesis blocks cell proliferation

Question 22

What is Lesch-Nyhan syndrome?

Answer 22

Hereditary syndrome

Severe or complete deficiency of HGPRTase activity

Results in hyperuricemia - causes tiny, orange crystals of sodium urate in infant’s diapers

Also results in uric acid stones, intellectual disability, and self-injurious behavior (biting fingers)

Question 23

What drug can help with fungal infections by fungi like Cryptococcus neoformans? Caused headache, nausea, fatigue, and altered mental state

Answer 23

Flucytosine

Systemic fungal infection prevalent in those with compromised immune systems (AIDS, patients on immunosuppressants)

Flucytosine (5-fluorocytosine) is an analog of cystine. Fungi express cytosine deaminase (humans do not). This enzyme converts cytosine/5-fluorocytosine to 5-fluorouracil which is then converted to FUMP. 5-fluorocytosine is toxic to fungi and relatively non toxic to humans

Question 24

Chronic Granulomatosis Disease

Answer 24

Deficiency in NADPH oxidase in phagocytes

Leads to recurrent infections because NADPH oxidase is activated in response to bacterial infection

Question 25

Where is iron found in the body?

Answer 25

Iron found in tetrapyrroles (heme, cytochromes) Bound to ferritin (cell storage) Bound to transferrin (blood transport)

Question 26

What are diseases leading to iron overload?

Answer 26

Hereditary hemochromatosis Thalassemia (alpha and beta) Sickle cell anemia Frequent blood transfusions

Question 27

What is hereditary hemochromatosis?

Answer 27

Mutation in HFE gene Causes excessive iron accumulation in tissues and organs Leads to organ destruction

Question 28

How does thalassemia (alpha and beta) and sickle cell anemia lead to iron overload?

Answer 28

Leads to excessive destruction of red blood cells causing iron overload

Question 29

What is amyotrophic lateral sclerosis (ALS)?

Answer 29

Deficiency in Cu/Zn-superoxide dismutase (SOD1) or misfolded Cu/Zn-SOD1 (sporadic) Progressive degeneration of motor neurons Leads to muscle weakness, paralysis, death within 3-5 years of diagnosis (adult onset)

Question 30

Where is adipose CT present in a fatty heart?

Answer 30

Present along other parts of the heart's surface other than in sulci/grooves or surrounding coronary vessels

Question 31

What is thickness of epicardial fat on heart surface positively correlated with?

Answer 31

Obesity Diabetes 2 Pro-inflammatory cytokine level Vascular aging Subclinical atherosclerosis

Question 32

What occurs to contractile cardiomyocytes after a myocardial infarction?

Answer 32

During and following a MI, contractile cells in the affected part of the myocardium undergo necrosis Rupture of membranes releases cardiac-specific troponin T and troponin I into surrounding ECM, which goes to tissue fluid, lymph vessels, and then blood Serum troponin T levels are elevated about 2-3 hours following chest pain onset and peak 12-48 hours

Question 33

What can cause an arrhythmia?

Answer 33

Abnormalities in the spatial distribution of gap junction in intercalated discs

Question 34

What is ANP?

Answer 34

Atrial Natriuretic Peptide

Question 35

What is BNP?

Answer 35

B-type natriuretic peptide

Question 36

what are the serum levels of ANP and BNP during congestive heart failure?

Answer 36

Both are elevated Heart still is beating, but is weak and cannot pump enough blood to meet oxygen demands ANP and BNP increase kidney filtration rate by natriuresis (increased sodium excretion) and diuresis (increased fluid excretion) Both ANP and BNP are vasodilators

Question 37

What is BNP a more sensitive biomarker of?

Answer 37

Heart failure Especially left ventricular dysfunction because levels of BNP increase as failure worsens Used to track treatment progress

Question 38

What is SARS-CoV-2 infection associated with?

Answer 38

Can trigger myocarditis (inflammation of the myocardium) Estimates of incidence vary greatly, but it occurs even in asymptomatic of mildly symptomatic patients (including children and athletes) and can occur following COVID-19 vaccination Also associated with: Fibrin clots and microclots (platelet clots) in myocardium capillaries Recruitment of megakaryocytes to myocardium Clotting of myocardium capillaries can cause localized tissue damage (ischemia)

Question 39

What does pacemaker cells and heart rate have to do with each other?

Answer 39

Number of SA nodal cells (pacemaker cells) determines maximum HR

Question 40

What does SA nodal cell do with age?

Answer 40

SA nodal cell number decreases with age - progressive slowing of conduction velocity and voltage loss Highest number of SA nodal cells in fetuses - this is why fetal HR is so high Reduction in SA nodal cell number drives the decrease in max (and target HR) that occurs with age This is a reduction in intrinsic heart rate - it happens whether sedentary or active, even in elite athletes

Question 41

What are Purkinje fibers vulnerable to?

Answer 41

Vulnerable during infection of the endocardium (ex. infective endocarditis (microbial infection of the endocardium)) Subendocardium is very close to the chamber lumen and Purkinje fibers are critical for heart function

Question 42

What does having extra glycogen make Purkinje fibers more resistant to?

Answer 42

Resistant to hypoxia vs contractile cardiac cells

Question 43

Valvular Degeneration

Answer 43

Valves with comprised structure have compromised function Valvular diseases often result in inefficient blood flow - patent valve (too much flow when shut), stenosis (too little flow when open), and valvular regurgitation (backflow) Consequence of valvular degeneration - cardiac muscle tissue is often weakened from the extra strain caused by inefficient blood flow through the heart

Question 44

What is important about pericytes and how they can differentiate into fibroblasts, smooth muscle cells, and endothelial cells?

Answer 44

Important role during blood vessel formation and repair - these are the cells you would need to synthesize a new endothelium, tunica media (smooth muscle), and tunica externa (CT)

Question 45

What are continuous capillaries necessary for given their solid walls?

Answer 45

Necessary for proper function of the blood-brain barrier and blood-gas barrier (alveolar wall in lungs)

Question 46

What are varicose veins?

Answer 46

Weakened or incompetent valves allow blood to pool or backflow in veins Valves stays partially open Instead of being pushed toward the hear, blood backflows (gravity) Blood settles in valve leaflets, pools, and causes bulging

Question 47

What is often used as a coronary artery bypass graft?

Answer 47

Great saphenous vein Because it has thick and muscular walls and is of similar size to coronary arteries

Question 48

How does edema relate to lymphatic drainage?

Answer 48

Tissue edema occurs when the capacity for lymphatic drainage is exceeded: Hydrostatic pressure is too high Oncotic pressure is too low Lymph capillaries are damaged or blocked (lymph flow impeded)

Question 49

What occurs with patients with low levels or malformed von Willebrand factor?

Answer 49

Have bleeding problems Clots either take longer to form or form incorrectly Leads to easy bruising, heavy menses, and bleeding gums

Question 50

What is von Willebrand disease?

Answer 50

Most common hereditary blood clotting disorder Affects 1% of the population worldwide, affects men and women equally Severity of bleeding varies by subtype

Question 51

What are the effects of aging on the aorta?

Answer 51

The number of elastic lamellae in the tunica media increases from birth to adult age

Question 52

What are the effects of aging on all elastic arteries?

Answer 52

Moderate intimal fibrosis - thickening of tunica intima by addition of collagen I fibers Minor fragmentation of elastic lamellae (media) - elastin protein starts to break down and wear out

Question 53

Acute tonsillitis

Answer 53

Infectious mononucleosis (mono) Caused by Epstein Barr virus and spread via saliva Fatigue and fever Severe pharyngitis (inflammation of pharynx) usually with tonsillitis (inflammation of tonsils) Lymph nodes also usually swollen and splenomegaly

Question 54

DiGeorge Syndrome

Answer 54

Patients are born with cleft palate and have other distinct facial features Leads to absence/hypoplasia of the parathyroid glands and the thymus Lack of thymus causes severe T cell deficiency or complete absence of T cells. Patients lack a cell mediated immune response, resulting in frequent and recurring infections Allergic and autoimmune manifestations Higher risk of some autoimmune conditions Absence of parathyroid glands cause issues regulating calcium (too low) and phosphorus (too high)