UW Flashcards
How to Dx asthma?
Px & Hx
Spirometry ( FEV1 & PEF).
If spirometry is normal = methacholine challenge test.
How to interpret methacholine challenge test?
It’s a muscrinic cholinergic agonist.
Causes bronchoconstruction and increased airway secretions.
I.e FEV1 by >20%.
What’s scopolamine?
What is it used for?
Muscarinic receptor antagonist.
Used for motion sickness.
What’s phenoxybenzamine?
What does it treat?
It’s a non-selective a-adrenergic antagonist.
Used in pheochromocytoma.
What’s asthma?
Obstructive airway disease.
Hypersensitivity of conducting airways to stimuli.
Karyotype of turner’s?
45 XO
Clinical features of turners?
Menarche?
Labs?
Short stature Thickened neck Square chest Widely spaced nipples. No breasts. Normal sexual hair distribution. No menarche.
High LH & FSH.
Can turner’s become pregnant?
They have ovarian failure, can’t.
Can use IVF with donor oocyte.
Need supplementation with estrogen & progesterone to maintain uterine lining.
What risk pregnancy has on turner’s women?
- What’s your action?
Aortic dissection or rupture.
Must evaluate cardiac & renal function throughout pregnancy.
What are the signs of DKA?
Mental status changes Dehydration Abdominal pain Tachypnea Fruity odor of breath.
+
Metabolic acidosis & high AG.
What are the finding of DKA on ABG?
Metabolic acidosis
With high anion gap.
PH
Treatment of DKA?
How does it work?
Insulin & hydration with NS.
• Insulin:
Utilization of glucose > lipolysis > normalizes glucose & stop Keton bodies = increased HCO3.
Intercellular shift of K = K in blood.
• NS:
Normalizes Na in blood & decreases osmolality.
Describe ABG changes is hypoaldosternism (RTA IV)
Metabolic acidosis with normal AG.
Treatment of metabolic acidosis in hypoaldosternism?
How does it work on ions, acids & osmolality?
Exogenous mineralocorticosteroids.
- Na/H2O retention.
- H & K excretion > hypokalemia & ⬆️HCO3.
- Increases serum osmolality.
How does loop diuretics affect ions, acids & osmolality?
• Decrease Na/H2O retention:
Low Na, low fluids > high serum osmolality.
- Loss of K = Hypokalemia.
- Retains HCO3.
What causes fruity smell of breath and urine in DKA?
Excretion of acetone
What 2 acids accumulate in DKA?
B-hydroxyburate
Acetoacetate
What’s minute ventilation?
How is it calculated?
It’s the volume of air that enters the respiratory pathways per minute.
Minute Volume = tidal volume x RR
What’s alveolar ventilation?
How is it calculated?
Volume of air reaching alveoli per minute i.e doesn’t include dead space.
Alveolar ventilation = (Tidal volume - dead space) x RR
What’s physiologic dead space?
How is it calculated?
Anatomical (conducting airways) and alveolar (well ventilated but poorly refused alveoli) dead space.
Physiological dead space = tidal volume x ([PaCO2 - PeCO2] / PaCO2)
During what stage of cardiac cycle does most of blood supply to myocardium occur?
What’s the major factor affecting myocardial blood flow?
Why?
80% of blood supply is during diastole
And depends mostly on duration of diastole.
Why?
Systole => the open aortic valve partially blocks coronary flow and coronary arteries are compressed by the contracting myocardium.
What happens to cardiac supply during exercise?
⬆️ HR and ⬇️ diastole
> more demand and less time to provide oxygen.
Adenosine (from ATP) vasodilates coronary vessels and increases blood flow.
What’s the type of inheritance in CF?
Autosomal recessive
Where’s the defect in CF?
Cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7.
F508 mutation.
What’s the F508 mutation?
What does it cause?
Deletion of 3 nucleotides coding for phenylalanine at position 508 of the CFTR protein.
Causes CF.
What’s the CFTR transmembrane protein and what does it pump?
How is it related to mucosal surfaces?
An ATP-binding cassette transmembrane ion transporter.
Pumps Cl out of epithelial cells against its concentration using ATP hydrolysis for energy.
By pumping Cl it creates a membrane potential that draws Na and H2O which hydrates mucosal surfaces like bowels and airways.
What’s the role of CFTR protein in sweat formation?
It plays a role in forming a hypotonic sweat.
Sweat is initially isotonic with the plasma, during transport through the ducts Na is removed from the ductal lumen by CFTR.
What’s the effect of CFTR defect on sweat in CF patients?
CF patients have high Cl in sweat
What test is used to screen for CF?
Sweat Cl Test.
Where are voltage-gated channels commonly found?
In neurons.
What’s the function of LH in males?
Stimulates the release of testosterone from the lyeding cells.
Where is LH released from?
Gonadotroph cells in the anterior pituitary.
What’s the function of FSH in males?
Release of inhibin B from the Sertoli cells in seminefrous tubules.
What’s the karyotype of Turners Syndrome?
45, XO (loss of paternal Ch X)
Classic Characteristics of newborn with turner’s syndrome?
- Cystic Hygroma = posterior neck mass of cystic spaces.
- Lymphedema = Bilateral extremities swelling.
- Coarctation of aorta = diminished femoral pulses.
What’s the pathology in congenital adrenal hyperplasia?
What’s the most common enzymatic defect?
Abnormal sexual differentiation due to defective hormone synthesis.
Most common enzymatic defect = 21-OH deficiency.
How do newborn with congenital adrenal hyperplasia present?
Girls have ambiguous genitalia and salt wasting (hypotension & low Na)
What’s the cause of pathology in androgen insensitivity syndrome?
Defective testosterone receptors.
What is the karyotype in androgen insensitivity syndrome?
46, XY
How do patients with androgen insensitivity syndrome present? (Phenotype)
Adolescent 46,XY how appears phenotypic ally female, has primary amenorrhea.
Presence of cryptorchid testes.
What’s the cause of primary amenorrhea in androgen insensitivity syndrome?
Absence of internal female reproductive tract.
What’s the cause of pathology in Trisomy 18 (Edward Syndrome)?
Meitotic nondisjunction.
Mention some of the symptoms of Trisomy 18?
Cardiac defects. Clenched fists. Rocker bottom feet. Omphalocele. Low set ears.
What’s the cause of pathology in Cri-du-chat?
Deletion of the short arm of Ch 5 (p5-)
What is the cause of pathology in Trisomy 21?
Meiotic nondisjunction
Robertsonian translocation.
What’s the mode of inheritance in Fragile X?
X-linked.
What’s the molecular cause of pathology in Fragile X?
Increased number of trinucleotide repeats (CGG) in familial mental retardation gene (FMR-1)
What are the symptoms of Fragile X syndrome?
• Body Habitus:
- Macrosomia => increased head circumference.
- Large jaw.
- Large protruding ears.
- Long thin face.
- prominent forehead.
- Large testis.
• Cognitive impairment:
- mental retardation.
- Language delay.
- Behavioral abnormalities (aggressiveness).
- Autistic features.
What’s Genome Recombination?
Gene exchange between 2 chromosomes that occur via crossing over within homologous regions of 2 ds-DNA.
What’s genome re-assortment?
Changes in genomic composition.
In viruses its when 2 segmented viruses exchange whole genome segment.
What’s the embryonic origin of SVC?
Common Cardinal veins
On an chest CT, how do you identify the SVC?
- Right to the heart
- Posteriolateral to ascending aorta.
- Anterior to Rt pulmonary artery.
- Below the carina.
Where do veins in embryo drain into?
Sinus venosus => primitive atrium.
What are the main categories of veins in embryo?
What do they give rise to after birth?
• Vitelline, umbilical & Cardinal veins.
• umbilical vein = degenerates.
Vitelline vein = veins of portal system.
Cardinal veins = veins of systemic circulation.
What develops from the truncus arteriosus?
Ascending aorta & pulmonary trunk.
What gives rise to descending aorta?
Fusion of embryonic Rt&Lt dorsal aortas
How does truncus arteriosus form the ascending aorta & pulmonary trunk?
- Migration of neural crest cell migration = fusion & twist of truncal & bulbar ridges.
What causes opening snap in MS?
Abrupt halting of leaflet motion during mitral valve opening due to fusion of leaflet tips.
What’s the most common cause of MS?
Rheumatic carditis.
What’s the murmur of MS?
Opening snap followed by diastolic rumble
At the apex of the heart.
What’s paroxysmal supraventricualr tachycardia?
What patients get this commonly?
Abrupt episodic onset of rapid HR and termination.
Due to re-entrant impulse traveling through rapidly and slowly conducting segments of AV node.
Patients with no heart disease.
Ex of Paroxysmal supraventricualr tachycardia?
1) Cardiac parasympathetic stimulation
> carotid sinus message & valsalva maneuver.
> parasympathetic => prolonged AV node refractory period => slow conductance through AV => Slow HR.
2) Adenosine
Compression of hypertrophic / dilated left atrium presents as?
Dysphasia
What are the 4 major divisions of the aorta & what’s their anatomical position?
- Ascending aorta = posterior & Rt to the main pulmonary artery
- Aortic arch = above the right pulmonary artery & left bronchus.
- Descending thoracic = left anterior surface of vertebral column & posterior to esophagus and left atrium.
- Descending abdominal = crosses diaphragm & branches into common iliac arteries.
How is the position of thoracic aorta helpful in TEE?
It lies posterior to esophagus & left atrium
Allowing clear visualization during TEE, which helps in detecting dissections or aneurysms.
Penetrating injury to left-sternal border in 4th ICS will pass through what layers?
- Skin & subcutis
- Pectoralis major
- External intercostal membrane
- Internal intercostal muscle.
- Internal thoracic artery & vein.
- Transverse a thoracis muscle.
- Parietal pleura.
- Pericardium.
- Rt ventricular myocardium.
Penetrating injury to 2nd intercostal space result in injury to?
Pulmonary trunk
Stab wound to 4th ICS midclavicualr line injures what structures?
Left lung & left ventricle.
Most common cause of blunt aortic injury?
Mechanism of injury?
Most common site of rupture? Why?
Dx?
Motor vehicle collisions
Sudden deceleration.
Aortic isthmus, tethered by ligamentum arteriosum => fixed and immobile.
Widened mediastinum on CXR.
Drugs that cause long QT interval?
Hint: ABCDE
Antiarrythemics (Class IA + III) Antibiotics (macrolides) Anti-psychotics (haloperidol) Anti-depressant (TCA) Anti-emetics (ondansetron)
What are the HMG-CoA reductase inhibitors?
What’s their mechanism of action?
Most common side effects?
- lipid lowering agents (Statin group)
- Inhibit the conversion of HMG-CoA to mevalonate (cholesterol precursor).
Work mainly on LDL. - Hepatotoxicity (high LFT)
What’s supine hypotension syndrome?
What’s the cause?
Who usually gets it?
Hypotension, sweating, nausea & dizziness when a pregnant woman lies supine.
Secondary to the uterus compressing IVC leading to reduced venous return and low CO & hypotension. Syncope if sever.
Pregnant ladies > 20 wks gestation.
What equations are used to calculate the CO?
- CO = HR x SV
- Fick Principle.
CO = O2 Consumption / arteriovenous O2 difference. - Using Hb & body surface area.
CO = (135 x BSA) / [(13 x Hb) x (SaO2 - SvO2)].
What’s the Resp quotient?
What’s its normal value?
What’s it used for?
It’s the ratio of CO2 to O2 across alveolar membrane.
Normal value 0.8
Used to estimate metabolic rate.
What allows pacemaker cells in the heart to exhibit automaticity?
The slow inward Na current (funny current) during phase 4.
How is the IVC formed and where does it drain?
IVC is formed by the Union of the art & Lt common iliac veins at the level of L4-5.
Drains into the Rt atrium at level of T8.
Thoracic vs cystic duct.
Function
Anatomical location.
- Thoracic duct:
- Drains lymph from the entire left side of the body and all regions inferior to umbilicus.
- enters the thorax through the aortic hiatus & empties into the left subclavian vein near its junction with internal jugular vein.
- Cystic Duct.
- drains bike from the gallbladder into the common bile duct.
- it lies just below the liver in the anterior Rt abdomen.
What makes up the portal vein?
Where is it anatomically?
- joining of superior mesenteric vein & splenic vein.
- near the head of pancreas.
Where do renal arteries originate anatomically? (Vertebral level)
Level L1.
How does the body respond to hypovolemic shock?
After losing 10% of circulating volume sympathetic nervous system is activated and leads to:
- Construction of arterioles:
Increase TPR
Maintain end-organ pressure & shunt the blood from extremities & skin to vital organs. - Construction of veins:
Increases VR and maintain preload. - Stimulation of the heart:
Increases contractility and HR.
What’s the mainstay treatment in hypovolemic shock?
What’s the mechanism of action?
- rapid infusion of blood products & NS
- IVF increase intravascular volume & ventricular preload.
Increased preload = extended end diastolic sarcomere length = high SV & CO.
What’s the cause of high TPR in hypovolemic shock?
Sympathetic stimulation.
What’s the effect of IVF on HR & TPR in patients with hypovolemic shock?
Decrease HR & TPR.
By reducing sympathetic activation.
What effects ventricular compliance?
Increases by = dilated cardiomyopathy.
Decreased by = amyloid deposition & hypertrophic cardiomyopathy.
Holo systolic murmur is characteristic of what heart disease?
How do you differentiate them?
Mitral & tricuspid regurgitation and VSD.
TR is associated with increased intensity during inspiration while MR & VSD are not.
TR is heard at left eternal border at 4th ICS.
MR is at 5th ICS midcalvicular line.
VSD at 3rd/4th ICS left sternal border.
What causes increased intensity of TR murmur during inspiration?
During inspiration intra-thoracic pressure drops, allowing more blood to return to Rt heart > Rt ventricular SV increases > increased capacity of Rt pulmonary vessels > low VR to left ventricle.
What’s the effect of the following on cardiovascular:
- NO
- Adenosine
- Norepinephrine
- Ach
- Ang-II
- Histamine
- Serotonin
- NO:
From endothelium.
Vasodilator of large coronary vessels. - Adenosine:
From ATP metabolism.
Vasodilator of small coronary vessels. - Norepinephrine:
Neurotransmitter released from SNS to stimulate alpha-receptors.
a1-receptors > construction of vessels.
a2-receptors > inhibit sympathetic system centrally.
B1-receptors > cardiac excitation. - Ach:
Neurotransmitter from PNS. Acts on muscarinic receptors > inhibitory effect on heart. - Ang-II
Powerful vasoconstrictor. - Histamine:
From mast cells.
Potent vasodilator - serotonin:
From neuroendocrine cells, platelets, serotonergic neurons.
Both vasodilation & constriction.
How & where is NO made?
How does it act?
When is it released?
It’s made by endothelial cells.
It’s synthesized from arginine and oxygen by enzyme eNOS (endothelial nitric oxide synthase.
Vasodilates vessels via guanylate cyclase enzyme to increase the production of cGMP & cause ms relaxation.
Released in response to:
- Neurotransmitters (Ach & NE)
- PLT products (serotonin, adenosine & diphosphate).
- Thrombin
- Histamine
- Bradykinin
- Endothelin.
- Pulsatile stretch & flow shear stress.
What’s the function of AV node?
Has a refractory period to regulate the number of atrial impulses that reach the ventricle and determines the ventricular rate.
What’s the pathology in A-Fib?
Characteristic ECG?
Aberrant electrical impulses that arise within regions of high atrial excitability (pulmonary veins) > electrical remodeling & shortened refractory periods with increased conductivity.
Resulting in persistent ectopic foci & re-entrant impulses within the atria.
Characteristic ECG: absent P waves, irregular R-R intervals & narrow QRS complexes.
What determines the duration of QRS complex ?
Bundle branch conductivity.
Thus when there’s a branch block QRS is widened.
What vessels supply myocardium?
Rt & Lt coronary arteries which originate from the root of aorta behind the 2 cusps of aortic valve.
Where do the coronary veins drain?
Coronary sinus in right atrium.
What features distinguish coronary from systemic circulation?
- Cardiac muscles is mostly prefixed during diastole & consumes 5% of CO.
- Cardiac oxygen extraction reaches 75 - 80% of oxygen content at rest and 90% at demand.
- Flow regulated by local metabolites NO, adenosine, Beta adrenergic activity for vasodilation
Alpha adrenergic for vasoconstriction.
Which is more deoxygenated:
Pulmonary artery or coronary sinus?
Why?
Coronary sinus.
Blood from coronary sinus which is extremely deoxygenated is mixed with blood from IVC which is less deoxygenated and thus the blood in pulmonary artery contains a mixture of the 2 and is less deoxygenated from the coronary sinus blood.
What’s the effect of AV shunt of pressure-volume loop?
1) AV shunts increase preload => increase rate and volume of VR.
2) AV shunts allow blood to bypass the arterioles => low TPR.
So elongated diastolic filling phase, high EDV and low after load.
What’s the end result of AV shunt?
High output heart failure.
What determines resting potential in cardiac muscle?
Membrane permeability for K
What’s the benefit of highly negative resting potential in cardiac muscle?
Reduce risk of arrhythmias.
What characterizes plateau phase in cardiac muscle AP?
Opening of L-type dihydropyridine-sensitive Ca channels
Closure of K channels.
Relate each pharyngeal arch with its corresponding aortic arch, CN & derivatives.
• 1st pharyngeal arch:
1st Aortic arch => maxillary artery
Trigeminal nerve CN V
• 2nd Pharyngeal arch:
2nd aortic arch => Stapedial artery.
Facial nerve CN VII
• 3rd Pharyngeal Arch:
3rd aortic arch => common carotid artery & proximal internal carotid
Glossopharyngeal CN IX.
• 4th Pharyngeal Arch:
4th aortic arch => true aortic arch & subclavian arteries.
Superior laryngeal branch of vagus.
• 5th Pharyngeal Arch:
Obliterated
• 6th Pharyngeal Arch:
6th aortic arch => pulmonary arteries & ductus arteriosus.
Recurrent laryngeal branch of vagus.
Define the following terms: • Permissive effect • Synergic effect • Additive effect • Tachyphylaxis
1) Permissive:
One hormone allows another to exert its maximal effect.
I.e cortisol up-regulates a1-adrenergic receptors and augment catecholamines & Ang-II vasoconstrictive effect.
2) Synergistic effect:
The combined effect of 2 drugs exceeds the sum of the individual drug.
3) Additive effect:
The combined effect of 2 drugs equal to the sum of their individual effects.
4) Tachyphylaxis:
Decreased drug responsiveness in a short period following one or more doses (rapid tolerance)
What are the therapeutic uses of GnRH depending on frequency of administration?
Pulsatile GnRH agonists => stimulates LH & FSH => Rx infertility.
Constant GnRH or long lasting analogue => Suppress LH & FSH => Rx precious puberty, prostate ca, endometriosis & dysfunctional uterine bleeding.
What’s the function of GnRH?
Secretion of LH & FSH => development of dominant follicle in ovaries.
Mention the signaling pathway of insulin.
Insulin binds a-subunit of its the receptor => autophosphorylation of receptor => ctivation of tyrosine kinase => interaction with receptor substrate 1 & 2
What’s the effect of TNF-alpha on insulin?
How?
What other substances exhibit similar effect?
- causes insulin resistance.
- By phosphorylation of insulin receptor substrate 1 serine residues => inhibiting tyrosine phosphorylation => insulin resistance.
- substances the phosphorylate threonine residues = catecholamines, glucocorticoids, glucagon.
What inactivates cAMP?
Hydrolysis of phosphodiestrase
What’s hydroxyproline used for?
How is it formed?
- used in synthesis of bone, skin & collagen.
- formed by hydroxylation of proline which requires vit c
What’s peroxisome proliferator-activated receptor gamma (PPAT-gamma)?
What’s its effect on insulin?
What drugs activate it?
It’s a nuclear receptor that alters gene transcription.
Improves insulin sensitivity.
Oral anti-diabetics (thiazolidinediones TZD).
What’s lecithin-sphingomyelin ratio used for?
Marker for fetal lung maturity.
> 1.9 indicative of mature lung.
What factors fetal lung development and how?
By increasing surfactant.
Glucocorticoids (most imp) Prolactin Insulin Estrogen Androgen Thyroid hormones Catecholamines
What’s the function of thyroid perixidase?
Catalyzing enzyme
- Oxidation of iodide into iodine.
- Coupling of TID & MID.
Antibodies against thyroid peroxidase result in what disease?
Hashimoto’s
What are the basic amino acids?
Lysine, arginine & histidine.
What’s the function of aromatase enzyme?
Converts androgens (androstenedione) to estrogen & testosterone to estradiol at the peripheral tissues.
Clinical manifestations of aromatase deficiency on mom & baby.
- Mom => virilization e.g hirsutism.
- Baby girl => normal internal female genitalia & ambiguous external genitalia (clitormegaly & pseudohermaphrodism)
At puberty => primary amenorrhea, osteoporosis & tall stature.
What’s the effect of 5a-reductase deficiency?
Decreased dihydrotestosterone in male.
=> undeveloped external male genitalia
