Physiology Flashcards
CO formulas (SV, HR, MAP, TPR)
CO = SV x HR MAP = CO x TPR (P = Q x R)
Pulse pressure formula
5 causes of increased pulse pressure
3 causes of decreased pulse pressure
pulse pressure = systolic pressure - diastolic pressure
Increases: hyperthyroidism, AR, aortic stiffening, OSA, exercise
Decreases: AS, post-MI shock, cardiac tamponade
What 3 factors change stroke volume?
CAP: contractility, afterload, preload
What 3 factors increase contractility? CND
catecholamines: increased Ca pump in SR, therefore increased [Ca]i
decreased [Na]e: decreased activity of Na/Ca exchanger (increased [Ca]i)
Digoxin: decreased Na/K pump –> incr. [Na]i –> decreased Na/Ca, incr. [Ca]i
What 4 factors increase myocardial oxygen demand?
increased with CARD: contractility, afterload, rate, diameter of ventricle
increased with wall tension (which = P x r / 2 x thickness)
increased afterload –> increased wall thickness to decrease wall tension and decrease O2 demand
What value approximates preload?
- approximated by ventricular EDV
- depends on venous tone, circulating blood volume
What value approximates afterload?
- approximated by MAP
Starling curve axes
stroke volume or CO vs. ventricular EDV
note: a left shift (increased CO for a given EDV) corresponds to an increase in contractility
Systemic resistance (R)
Give formulas and facts
P = Q x R (R = P/Q) Q = v x A
capillaries are highest cross-sectional area, lowest velocity
arterioles form the majority of TPR (organ removal = increased TPR, lead to decreased CO)
CO/preload interplay
inotropy, venous return, TPR
Inotropy: alters CO for a given preload
Venuos return: alters preload for a given CO
TPR: altered CO for a given preload
exercise: incr. inotropy, decr. TPR = increased CO
fluid retention: decr. inotropy, incr. preload = increased CO (to compensate for HF)
Contraction phase cycle
graph shows relationship between LV pressure vs. LV volume
1: isovolumetric contraction
2: systole
3: isovolumetric relaxation
4: diastole
increased contractility = decr. ESV (higher SV), left expansion
increased preload = incr. EDV (higher SV), right expansion
increased afterload = increased ESV (lower SV), narrowing from the left
Heart sounds
S1: mitral/tricuspid closure
S2: atrial/pulmonic closure
S3: increased flow velocity in early diastole (due to dilated ventricular chamber)
S4: heard in late diastole due to atrial kick
JVP waveforms
a = atrial contraction c = RV contraction x = atrial relaxation v = filling of right atrium y = right atrium emptying into right ventricle
JVP characteristics on physical exam
multiphasic, non-palpable, occludable
S2 splitting (normal, wide, fixed, paradoxical) aortic vs. pulmonic valve closure
normal: incr. venous return w/ inspiration –> delayed PV closure
wide: pulm stenosis, RBBB –> delayed RV emptying
fixed: ASD –> const. incr. RV volume –> delayed PV closure
paradoxical: aortic stenosis, LBBB –> delayed aortic closure (pulmonic closes first! therefore paradoxical), gap closes on inspiration instead of widening
L sternal border auscultation
best for diastolic murmurs (eg. AR), or hypertrophic cardiomyopathy
Effects of bedside maneuvers Inspiration Hand grip Valsalva Rapid squatting
Inspiration: incr. venous return, incr. intensity of R heart sounds
Hand grip: incr. afterload, incr. intensity of MR/VR/VSD
Valsalva (phase 2): decr. preload, incr. hypertrophic cardiomyopathy
Rapid squatting: incr. venous return, increased AS murmur, decr. hypertrophic cardiomyopathy
Systolic heart murmurs Aortic stenosis Mitral regurg Mitral valve prolapse VSD
AS: Crescendo-decrescendo (peripheral pulse is late and weak)
MR: holosystolic blowing
MVP: late systolic crescendo w/ click
VSD: holosystolic, harsh
Diastolic heart murmurs
Describe sounds
AR: high-pitched blowing
MS: opening snap, rumbling late
Myocardial action potential
Phase 0: depol = opening of fast Na channels (influx)
Phase 1: inactivation of Na channels, opening of K channels (efflux)
Phase 2: opening of Ca channels (influx, L type), plateau
Phase 3: rapid repol, close of Ca channels, opening of slow K channels (efflux)
Phase 4: resting = K+ ep. pot., high K permeability
Cardiac vs. skeletal potentials
- ) Plateau in cardiac cells
- ) SR initiates in skeletal
- ) cardiac nodal cells spontaneously depolarize due to funny current
- ) cardiac myocardium are electrically coupled through gap junctions
Pacemaker cell potentials
Phase 0: upstroke, opening of Ca
Phase 3: Ca inactivate, then incr. K efflux
Phase 4: slow Na influx (funny current slowly depolarizes)
Funny current variables
Ach/adenosine = decreased HR catecholamines = increased HR
Congenital long QT syndrome
usually due to ion channel defects
sometimes seen with deafness
Brugada syndrome
Asian males, pseudo-RBBB, V1-V3 ST elevation
due to ion channel defect
tx: ICD
ANP vs. BNP
both: act via cGMP to vasodilate and decrease Na resorption by the kidney
ANP: increase with blood volume
BNP: increase with ventricular torsion
Aortic vs. carotid receptors
Aortic: located in arch, transmit through CN X
Carotid: located at bifurcation, transmit through CN IX
both to solitary nucleus in medulla
Baroreceptors stimulation
firing increases with stretch!
decreased stretch –> decr. firing –> incr. symp activation (BP, HP, etc.)
Carotid massage mechanism
Incr. pressure on carotid sinus = incr. stretch/incr. firing = incr. AV refractory period = decr. HR
Cushing reflex (incr. ICP, incr. BP, decr. HR)
incr. ICP –> cerebral ischemia –> incr. PCO2 –> symp reflex –> incr. BP –> incr. stretch –> decr. HR
Chemoreceptors (peripheral vs. central)
Peripheral: stimulated by decr. PO2, incr. PCO2, decr. blood pH
Central: pCO2, respond to levels in the brain interstitial fluid (CO2 flows better to bloodstream)
Insulin synthesis
Preproinsulin then…
RER: cleavage of signal peptide to proinsulin, folded and formation of disulfide bonds
Transport to Golgi
Immature granules: cleavage into insulin and C-peptide
Insulin packaged in mature granules for secretion
Insulin receptor
- bind tyrosine kinase receptors
Insulin secretion
Glucose enters B-cell through GLUT2
Increased ATP/ADP ratio closes K channel (less K efflux)
Depolarization leads to Ca influx (acitvates phospholipase C, increased IP3 to further increase intra Ca)
High [Ca]i leads to granule release
Prolactin function and regulation
- function: leads to milk production, decr. ovulation/spermatogenesis by decr. GnRH
- hypothalamus secretes DA (inhibits prolactin) and TRH (stimulates prolactin)
- prolactin inhibits GnRH, stimulates DA
GH function and secretion
linear growth, muscle mass and insulin resistance
Stimulated by GHRH during sleep and exercise
Appetite regulation
Ghrelin vs. Leptin
Ghrelin - stimulates hunger and GH release, produced by stomach
Leptin - satiety, produced by adipose, low in starvation, mutation = obesity
ADH synthesis and function
synthesized in supraoptic nucleus
V2 receptors: regulate serum osmolarity
V1 receptors: blood pressure
secretion regulated by osmoreceptors in the hypothalamus
17-OHase deficiency (decr. androstenedione)
- blocks progenitors from cortisol/sex hormone production, only aldosterone is made
- def = incr. aldosterone (incr. BP, K+ wasting), decr. sugar/sex hormones
21-hydroxylase deficiency (incr. 17-OH-P)
2nd step in aldosterone/cortisol synthesis
- def = increased sex hormones, decr. salt/sugar hormones (decr. BP, high serum K+)
11B-hydroxylase deficiency
3rd step in salt/sugar hormone synthesis
- def = incr. 11-DOH-C (incr. BP, K+ wasting), decreased aldosterone/cortisol, increased sex hormones
Cortisol functions (BIG FIB)
increase in: Blood pressure (incr. alpha receptors = incr. sens. to Epi/NorEpi), Insulin resistance, Gluconeogenic
decrease in: Fibroblast activity, Inflammatory/Immune responses, Bone building
Albumin-bound Ca and pH
increased pH (more basic) = more neg. charge on albumin = more bound Ca –> hypocalcemia
Vit. D effects
increased absorption of Ca and PO4 from gut
increased bone resorption from Ca and PO4
regulation: stimulated by PTH, low Ca, low PO4
PTH effects (give target organs, molecular mediators, and stimulators)
leads to increased serum Ca, decreased serum PO4
- kidney: incr. Vit. D, incr. Ca, decr. PO4 (so urine will have low Ca and high PO4)
- bone: release of Ca and PO4 (osteoclasts by RANK-L)
- increased MCSF and RANK-L
- stimulated by low Ca, high PO4, low Mg
Calcitonin effects
opposes PTH
tones down Ca levels by decreasing bone resorption of Ca
Sex-hormone binding globulin (effects of incr./decr. levels)
increased SHBG –> decr. free testosterone –> gynecomastia
decreased SHBG –> incr. testosterone –> hirsutism
pregnancy and OCPs increase SHBG levels
Thyroid hormones (effect on metabolism, effects of T3)
- control metabolic rate through Na/K ATPase activity (and thus O2 consumption)
T3: Brain maturation, Bone growth, B-adrenergic effects, Basal metabolism
TBG: decr. in hepatic failure, incr. in pregnancy
Iodine and thyroid hormones
T4 is converted to T3 by 5’-deiodinase (PTU blocks this also)
Thyroid peroxidase prepares idoine to be incorporated in T3 (PTU blocks this)
Gastrin (G cells in antrum)
Effects and secretion
increased H+ secretion, mucosa, motility
stimulated by food in the stomach
abnormally increased in H. pylori, Z-E, PPI use
Somatostatin (D cells in pancreas, mucosa)
decr. acid, decr. pancreatic/gall bladder secretions, decr. insulin/glucagon
Stimulated by acid
Cholecystokinin/CCK (I cells in duodenum)
increased pancreatic secretions, delayed stomach emptying
acts on neural muscarinics
Secretin (S cells in duodenum)
incr. HCO3, bile, decr. gastric acid
Allows for enzyme function in the duodenum
GIP (K cells in duodenum)
exocrine: decr. H+
endocrine: incr. insulin
motilin (small intestine)
incr. MMCs!
VIP
incr. water/electrolyte secretion
stimulated by vagal nerve
Parietal cell inputs and mechanisms for acid secretion
Ach, gastrin –> Gq –> IP3
histamine* –> Gs –> cAMP
Both increased H+/K+ ATPase
Prostaglandins, somatostatin –> Gi –> decr. cAMP
Gastric acid regulation
Stimulated by histamine, Ach, gastrin
Inhibited by somatostatin, GIP, prostaglandins
Pepsin (chief cells)
Protein digestion
vagal stimulation
pepsinogen –> pepsin in the presence of H+
HCO3- (mucosal cells and Brunner glands)
Neutralize acid
Is secreted and then trapped in the mucus lining the epithelium
Pancreatic secretions (give the 3 enzymes)
amylase - starch digestion
proteases are secreted as zymogens
trypsinogen - activates other proenzyes, requires activation by enterokinase and peptidase
Carbohydrate absorption (give 3 glucose transporters)
Monosaccharides only through SGLT-1 (Na-dependent)
Fructose through GLUT-5
Transferred to bloodstream through GLUT-2
D-xylose test
if intact mucosa, then absorbed and excreted in urine
if SIBO/Whipple’s, then decr. absorption and treated with Abx
if still not fixed, then structural deformity (eg. celiac)
Peyer patches
M-cells: APCs
B-cells transform to IgA-secreting plasma cells in the lamina propia
Bile production (give rate limiting step and three functions)
rate-limiting step: cholesterol 7-a-hydroxylase
functions: digestion, cholesterol excretion, anti-microbials
Bilirubin
macs: heme –> unconj. bilirubin (bound to albumin in blood)
liver: unconj. bili + albumin –> conj. bili
gut: conj. bili –> urobilinogen (20% reabsorbed, 10% of which is secreted in urine and 90% of which is sent back to liver in enterohepatic circulation)
liver enzyme: UDP-gluconyltransferase
Anticoagulants
Give the Xa inhibitors
Give the IIa (thrombin) inhibitors
Xa inhibs: LMWH*, heparin, rivaroxaban, fondaparinux
IIa inhibs: heparin*, LMWH, argatroban
Hemophilias
Give type and factor affected
All have lack of functional clotting factors
A: decr. 8
B: decr. 9
C: decr. 11
Describe the clotting pathways
Intrinsic: [12 –> 11 –> 9] –> 10 –> 2 (thrombin) –> 1 (fibrin)
Extrinsic: [7 –> 10]
Note: 8 (9 –>10) and 5 (10 –> 2) both require Ca and phospholipid
Platelet plug formation (give 5 steps and notable factors)
Injury: transient vasoconstriction
Exposure: vWF (WP bodies, alpha granules) binds exposed collagen
Adhesion: plts adhere by GpIb, release ADP, Ca, TxA2
Activation: ADP in plt –> GpIIb/IIIa
Aggregation: fibrinogen binds GpIIb/IIIa, links plts
Give thrombotic (platelet) anticoagulants
Aspirin = decr. COX-1 --> decr. TxA2 Clopidogrel = decr. GpIIb/IIIa
Ristocetin assay
normally ristocetin activates vWF to bind Gp1b
failure of agglutination during assay = vWF disease or Bernard-Soulier (decr. plt adhesion)
Describe 3 platelet defects
Glanzmann - decr. GpIIb/IIIa (decr. activation)
vWF disease
Bernard-Soulier - decr. GpIb (decr. adhesion)
Glomerular filtration (give 3 components of the barrier)
- ) fenestrated endothelium (size barrier)
- ) BM w/ heparan (neg. charge)
- ) podocyte foot processes
Clearance formula
Cx = (Ux times V) / Px
in words, clearance is equal to urine conc. times urine flow rate all over plasma conc.
If Cx > GFR, then net secretion
If Cx < GFR, then net reabsorption
GFR
GFR = Cinulin (inulin has no net secretion or reabsorption)
Also, GFR = Kf[(Pgc - Pbc) - (πgc - πbc)]
Normal = 100 mL/min
Creatinine overestimates due to slight secretion (clearance is abnormally elevated)
Effective renal plasma flow
eRPF = Cpah (PAH is freely filtered and secreted)
RBF = RPF/(1 - Hct)
- note: underestimated by 10%
Filtration fraction formula
FF = GFR /RPF (normal = 20%)
in words, the proportion of fluid entering kidney that then enters the tubules
This has to be manipulated in situations where the blood flow to the kidney itself is variable
Afferent/efferent arteriole physiology
Afferent dilation (prostaglandins): increased GFR/RPF, no effect on FF
Afferent constriction (symp NS): decreased GFR
Efferent constriction (Ang. II): decr. RPF, incr. GFR, incr. FF)
Glucose in the kidney
mainly reabsorbed in PCT by Na/glucose co-transporter
> 200 = glucosuria, >375 = saturation of transporters
Hartnup disease (amino acid transport)
Decreased AA transporters in the PCT –> neutral aminoaciduria
Leads to decr. tryptophan –> decr. niacin –> PELLAGRA
Tx: high-protein diet
Proximal tubule
give function and two compounds that act here
reabsorb glucose/AA/HCO3/Na/Cl/PO4/K/H20
- secretes NH4+ to maintain luminal charge
Ang II: incr. Na/H exchange, incr. Na/H2O/HCO3 absorption
Acetazolomide: decr. carbonic anhydrase –> decr. HCO3 reabsorption
Thin descending loop of Henle function
Water reabsorption according to medullary gradient
- aka concentrating segment
- NO SODIUM TRANSPORT
Thick ascending loop function
- Na/K/Cl reabsorption
- also, induced paracellular reabsorption of Ca/Mg
NO H2O transport!
Distal Convoluted Tubule
reabsorb Na/Cl
- site of the MOST DILUTE URINE
- PTH: increased Na/Ca reabsorption on basal/blood side
Collecting tubule
Give details of aldosterone/ADH effects
- reabsorb Na, secrete K
Aldosterone: nuclear receptor, increased mRNA to increased Na/K pump and ENaC on principal cell. Loss of lumen positivity leads to K wasting
ADH: through V2 receptors, leads to increased aquaporins on apical side
Fanconi anemia effects and causes
Generalized reabsorptive defects
Increased excretion of everything –> metabolic acidosis (Type 2/proximal RTA)
Causes: Wilson’s, ischemia, multiple myeloma
Bartter syndrome defect and effects
defect in Na/K/2Cl transporter in ascending limb
leads to hypokalemia, metabolic alkalosis, and hypercalciuria
Gitelman syndrome defect and effects
defect in Na/Cl transporter in DCT
less severe than Bartter
Liddle syndrome defect and effects
gain of function mutation in ENaC
- leads to hypertension, hypokalemia
tx: amiloride (ENaC inhibitor)
Apparent mineralocorticoid excess
11 B-OH dH leads to failure of cortisol –> cortisone
incr. cortisol –> activation of MC receptors
leads to HTN, K wasting
- acquired from licorice
RAAS sensors
- ) JG cells (respond to low BP) secrete renin
- ) macula densa (respond to low distal Na delivery) release adenosine
- ) B1 receptors (respond to incr. symp drive)
RAAS function
increased renin cleaves angiotensinogen to AT-1
ACE (from pulmonary endothelium) cleaves AT-1 to AT-2 (also breaks down bradykinin)
Effects of angiotensin-2 (six total)
Vasoconstriction: AT1 receptor of vascular smooth muscle
Efferent arteriole constriction: increased FF/GFR to preserve renal function
Aldosterone: principal cells (incr. ENaC, basal Na/K pump), alpha-intercalated (H+ ATPases)
ADH: increased aquaporins
PCT: incr. Na/H activity (incr. Na/HCO3, H2O reabsorption)
hypothalamus: stimulates thirst
Atrial natriuretic peptide
- acts on afferent arteriole to increase GFR
- also decreases Na reabsorption in the DCT
Renal tubular acidoses
give name, location, electroytes involved
Type I distal: alpha-intercalated, no new HCO3, decr. H secretion, assoc. with hypokalemia
Type II proximal: decr. PCT HCO3 reabsorption, hypokalemia
Type IV hyperkalemic: hypo-aldosterone leads to excess K, decreased NH4 secretion
- can be either an absolute reduction in aldosterone or aldosterone resistance
Estrogen sources and hormone secreted
Ovary: estradiol
Adipose: estrone
Placenta: estriol
Estradiol > estrone > estriol
Estrogen receptor
Expressed in cytoplasm
Translocates to nucleus when bound by estrogen
Estrogen functions
Development, increased estrogen/LH/progesterone receptors
increased SHBG, incr. HDL, decr. LDL
Incr. endometrial proliferation
Progesterone sources
Corpus luteum, placenta, adrenal cortex, testes
Progesterone function
stimulate endometrial glands and spiral arteries
Production of thick cervical mucus
incr. body temp, decr. endometrial proliferation
Oogenesis
primary oocytes: 2N, 4C, frozen in prophase I until ovulation (46 sister chromatids)
secondary oocytes: 1N, 2C, frozen in metaphase II until fertilization (23 sister chromatids)
Fertilization
Sperm entering oocyte triggers cortical reaction (prevention of another sperm from entering, continuation of second division, leading to extrusion of polar body)
Ovulation
increased estrogen past the inhibitory threshold leads to an LH surge, which induces ovulation (follicle rupture) and progesterone-induced rise in temperature
Fertilization must happen within 1 day, in the ampulla
Lactation (describe roles of prolactin and oxytocin)
Prolactin - induces milk production, decreases reproductive potential
Oxytocin - assists in milk letdown, promotes uterine contractions
hCG (give source and function)
source: syncytiotrophoblasts
function: maintian corpus luteum for first 8-10 weeks
incr. in twins, Down’s, moles
decr. in ectopic, Edward/Patau
Spermatogenesis
full cycle takes 2 months
spermatogonium: 2N, 2C (46 chromosomes), then become… (after leaving blood-testis barrier)
primary spermatocyte: 2N, 4C (46 sister chromatids)
secondary spermatocyte: 1N, 2C (23 sister chromatids)
Spermatid: 1N, 1C, then undergoes maturation (loss of cytoplasmic contents and gain of acrosomal cap) to become spermatozoon
Androgens (potency, function, conversion enzymes)
DHT > testosterone > androstenedione
testosterone: differentiation, growth spurt, voice, libido
DHT: penis, scrotum, prostate (then, balding, sebaceous glands)
5a-reductase: testosterone –> DHT
aromatase: convert androgens to estrogen in adipose tissue (estrogen helps close epiphyseal plates)
Lung volumes
Describe IC, ERV, VC
FRC is the base line (RV + ERV), and a normal breath in is the TV
Maximal inspiration from FRC = TV + IRV = IC
Maximal expiration from FRC = ERV
Maximal inspiration/expiration overall: ERV + TV + IRV = VC (vital capacity)
Physiologic dead space
give formula as well
Volume of air that does not participate in gas exchange
= tidal volume times (arterial CO2 - expired CO2)/arterial CO2
Hemoglobin
taut (low affinity) vs. relaxed (high affinity)
Taut in tissues! Therefore allows O2 unloading
- more taut = R shift (incr. H+, 2-3BPG, temp)
Relaxed in respiration! Therefore allows O2 binding
Methemoglobin
Oxidized Hb, increased affinity for CN
Causes by nitrites/thiosulfate, which is used to treat CN poisioning
Carboxyhemoglobin
Hb bound to CO, decr. O2 capacity, decr. O2 unloading
Hb dissociation curve (describe shape, shifts)
Hb: positive cooperativity (incr. O2 binding = incr. affinity) leads to higher binding potential
R shift = lower saturation for a given pO2, caused by incr. H+, temp, 2/3BPG
Oxygen content of the blood
Dissolved O2 + (Hb times 1.34 mLO2/gHb times %sat)
Note! O2 delivery = O2 content times CO
Pulmonary circulation
normally, low resistance with incr. compliance
Note, opposite reactivity from systemic circulation; low PaO2 (hypoxemia) –> vasoconstriction
Gas diffusion
In normal resting human: O2 and CO2 are perfusion-limited (PaO2 depends on flow rate)
In emphysema and fibrosis, O2 is diffusion-limited, and therefore doesn’t PaO2 does not equal PAO2 by the time blood leaves the capillary
Pulmonary vascular resistance
PVR = pressure in pulm. artery minus pressure in left atrium all divided by cardiac output (recall, R = deltaP/Q)
Alveolar gas equation
PAO2 = PIO2 - PaCO2/RQ = 150 - PaCO2/0.8
normal A-a gradient = 10-15 mmHg
incr. A-a gradient = V/Q mismatch, shunt, diffusion impairment
Hypoxemia
normal A-a: high altitude, hypoventilation
increased A-a: V/Q mismatch, shunting, diffusion impairment
CO2 transport (Haldane effect, Bohr effect)
90% as HCO3-, 5% as HbCO2, 5% dissolved
When O2 binds to Hb in the lungs, H+ is let go and forms CO2, allowing for unloading and expiration
In peripheral tissue, incr. H+ from metabolism leads to incr. O2 unloading
High altitude effects
incr. ventilation, decr. PaCO2, incr. EPO, incr. 2,3BPG (shift of curve to right)
also, incr. renal excretion of HCO3
