Physiology Brs Flashcards
Solution 150mM NaCl is …tonic
Isotonic
Solution 300mM mannitol is …tonic
Isotonic
At the muscle end plate ACh causes the opening of
Na and K channels
At the muscle end plate ACh causes …polarization to which value
Depolarization to a value halfway the Na and K equilibrium potentials
Why hyperkalemia causes muscle weakness?
Because Na channels are closed by depolarization
Function of γ-motoneurons
Innervate intrafusal myscle fibers –> adjust the sensitivity of the muscle spidle so that it will respond appropriately during muscle contraction
Decerebrate rigidity is caused by
Increased reflex muscle spindle activity due to removal of inhibition of higher centers
What kind of lesions cause decerebrate rigidity?
Lesions above the lateral vestibular nucleus and lesions above the pontine reticular formation but below the midbrain
The excessive muscle tone in decerebrate rigidity can be reversed by
Cutting the dorsal roots
Second order neurons in the olfactory pathway
Mitral cells
Low doses of epinephrine cause vasodilation/vasoconstriction?
Vasodilation (β2 more sensitive to epinephrine than α)
High doses of epinephrine cause vasodilation/vasoconstriction?
Vasoconstriction (μαλλον εχουν περισσοτερους α)
Conscious proprioception (below the lesion) after complete transection of the spinal cord
Permanently lost (because of the interruption of sensory fibers)
Stretch reflexes (below the lesion) after complete transection of the spinal cord
Temporarily lost (because of the spinal shock) , return with time or become hypersensitive
Dihydropyridine receptors (heart)
Voltage-sensitive protein of the T tubules, L-type channels. During the plateau of the action potential Ca2+ enters the cells from extracellular fluid through these channels
Ryanodine receptors (heart)
Ca2+ that enters the cell through the L-type channels (dihydropyridine receptors) triggers release of Ca2+ from the SR = Ca2+ -induced Ca2+ release)
Digitalis
Inhibits Na-K ATPase -> diminishes Na gradient -> diminishes Na-Ca exchange (that extrudes Ca) -> ^ intrac Ca
Pulmonary blood flow greater than aortic blood flow
Left-to-right ventricular shunt
A pattern of two P waves preceding each QRS complex indicates
Decreased conduction velocity in the AV node
The greatest pressure decrease in the circulation occurs across ______
because
Across the arterioles because they have the greatest resistance (ΔP= Q x R)
Cushing reaction
=response to cerebral ischemia.
^ intracranial pressure ->
compression of the cerebral blood vessels ->
cerebral ischemia (^ CO2) ->
sympathetic outflow to the heart and blood vessels ->
PROFOUND INCREASE IN ARTERIAL PRESSURE
Hering-Breuer reflex
Lung stretch receptors: distention of the lungs –> reflex decrease in RR
J (juxtacapillary) receptors
in the alveolar walls, close to the capillaries
Engorgement of the pulmonary capillaries (e.g. left heart failure) –> rapid, shallow breathing
Adaptation to high altitude
- respiratory alkalosis (acetazolamide)
- ^ EPO
- ^ 2,3-DPG
- Pulmonary vasoconstriction (hypertrophy if the right ventricle)
Mature levels of surfactant (can be reflected)
Lecithin:sphingomyelin ratio greater than 2:1
Major site of airway resistance in the lungs
Medium-sized bronchi
The smallest airways would seem to offer the highest resistance BUT parallel arrangement
Bohr effect
Increases in Pco2 / decreases in pH shift the curve to the right (e.g. during exercise: tissues produce more CO2)
Hemoglobin- O2 dissociation curve:
Shifts to the right
- increases in Pco2/decreases in pH
- increases in temperature
- increases in 2,3-DPG concentration
Hemoglobin- O2 dissociation curve:
Shifts to the left
- decreased Pco2/increased pH
- decreased temperature
- decreased 2,3-DPG (e.g. HbF)
- CO poisoning
Cause of hypoxemia
- decreased PAo2
- diffusion defect
- V/Q defects
- right-to-left shunts
Abnormal A-a gradient
>10mm Hg Causes: -diffusion defect -V/Q defects -right-to-left shunts
Causes of Hypoxia
- decreased cardiac output / blood flow
- hypoxemia
- anemia (decreased hemoglobin concentration)
- CO poisoning
- Cyanide poisoning
Pulmonary blood flow greater than aortic blood flow
Left-to-right shunt:
In normal adults,output of left ventricle=output of right ventricle. When defect in ventricular septum (left-to-right shunt) the “shunted” fraction of the left ventricular output is added to output of the right ventricle
Chemoreceptors in control of breathing
- CENTRAL
- Medulla : pH
- PERIPHERAL
- Carotid bodies : Po2 (if <60mm Hg) , Pco2
NH3 synthesis in acidosis
Adaptive increase in NH3 synthesis
(in the renal cells –> diffuses down its concentration gradient from the cells into the lumen –> combines with H+ to form NH4+ –> NH4+ is excreted)
TBW is highest in
Newborns and adult males
TBW is lowest in
Adult females and in adults with a large amount of adipose tissue
Major ions of ICF
Cations: K+ and Mg2+
Anions: protein and organic phosphates (ATP,ADP,AMP)
Substances with the lowest clearances
- not filtered: protein
- reabsorbed: Na+, glucose, amino acids, HCO3-, Cl-
Major ions of ECF
Cations: Na+
Anions: Cl- and HCO3-
Measuring the volumes of the fluid compartments-Markers
- Tritiated water: for TBW (wherever water is found)
- Mannitol: for ECF (too large to cross membranes)
- Evans blue: for plasma (binds to serum albumin)
Proximal tubule
EARLY Reabsorbs: -Na+ -H2O (TF/PNa+=1.0) -HCO3- -glucose -amino acids -phosphate -lactate
Secretes:
-H+
LATE
Reabsorbs:
-Na+ with Cl-
Water clearance = 0
During treatment with loop diuretics:
Inhibits NaCl reabsorption in the thick ascending limb—>
-inhibits dilution in the thick ascending limb
-inhibits production of the corticopapillary osmotic gradient
—>
URINE CANNOT BE DILUTED OR CONCENTRATED
Glomerulotubular balance
In the proximal tubule maintains constant fractional reabsorption (=67%) of the filtered Na+ and H2O ασχετα απο GFR
thanks to Starling forces, πc in the peritubular capillary blood
Thick ascending limb of the loop of Henle-Potential
Lumen-positive potential difference:
Although the Na+-K+-2Cl- cotransporter appears to be electroneutral, some K+ diffuses back into the lumen
Loop diuretics
Furosemide, ethacrynic acid, bumetanide
Inhibit the Na+-K+-2Cl- cotransporter at the thick ascending limb of the loop of Henle
Thiazide diuretics
Inhibit the Na+-Cl- cotransporter at the early distal tubule
How much of the overall Na+ reabsorption is affected by aldosterone?
About 2%
K+ -sparing diuretics
Spironolactone (antagonist of aldosterone)
Triamterene, amiloride (act directly on the principal cells)
Decrease K+ secretion in principal cells at the late distal tubule and collecting duct
Acetazolamide
Diuretic - Carbonic anhydrase inhibitor
In the early distal tubule by inhibiting the reabsorption of filtered HCO3-
K+ excretion
Can vary widely from 1% to 110%
Depending on dietary K+ intake, aldosterone levels and acid-base status (and flow rate)
K+ excretion
Can vary widely from 1% to 110%
Depending on dietary K+ intake, aldosterone levels and acid-base status and flow rate (e.g. thiazide increase flow rate at the site of distal tubular secretion –> K+ excretion is increased)
Causes of shift of K+ out of cells —> Hyperkalemia
Insulin deficiency β-adrenergic antagonists Acidosis Hyperosmolarity Inhibitors of Na+-K+ pump (digitalis) Exercise Cell lysis
Causes of shift of K+ into cells —> Hypokalemia
Insulin
β-adrenergic agonists
Alkalosis
Hyposmolarity
Increase of RBF
Caused by Vasodilation of renal arterioles produced by -prostaglandins E2 and I2 -bradykinin -nitric oxide -dopamine
Vasodilation of afferent and,to a lesser extent, vasoconstriction of efferent arterioles
Produced by
Atrial natriuretic peptide (ANP)
Buffers
Extracellular:
- HCO3- (CO2/HCO3- pK=6.1)
- Phosphate (H2PO4-/HPO4-2 pK=6.8) –> URINARY BUFFER
Intracellular
- Organic phosphates (AMP,ADP,ATP, 2,3-DPG)
- Proteins: imidazole, α-amino groups, Hemoglobin (deoxy)
Concentration of inulin in the tubular fluid reflects
The amount of water remaining in the tubule because inulin once filtered us neither reabsorbed nor secreted
Hypermagnesia
Hypocalcemia <—- increased Ca2+ clearance
Because Mg2+ competes with Ca2+ for reabsorption in the thick ascending limb
How alkalosis affects K+
Reduced [H+] in blood will cause intracellular H+ to leave cells in exchange for extracellular K+
Filtration fraction=
The fraction of RPF filtered across the glomerular capillaries
= GFR/RPF
normally about 0.20
Increases—>^protein concentration of peritubular capillary blood—> ^reabsorption in the proximal tubule
Decreases—> decreased protein concentration of peritubular capillary blood —> decreased reabsorption in the proximal tubule
D
How oxygen deprivation affects reabsorption in the proximal tubule?
Would inhibit reabsorption by stopping the Na+-K+ pump in the basolateral membranes
RBF=
RPF/1-Hct= Cpah/1-Hct = (Upah x V/Ppah)/1-Hct
Regulation of gastrin secretion
Stimuli for secretion:
-small peptides and amino acids
most potent phenylalanine and tryptophan
-distention of the stomach
-vagal stimulation mediated by gastrin-releasing peptide (GRP) NOT ACh!!! (not blocked by atropine)
Inhibition of gastrin secretion:
- H+ in the lumen of the stomach (negative feedback)
- Somatostatin
HCO3- reabsorption in metabolic alkalosis
Normally increased excretion of HCO3- because the filtered load of HCO3- exceeds the ability of the renal tubule to reabsorb it
BUT
If metabolic alkalosis is accompanied by volume contraction (e.g. vomiting) the reabsorption of HCO3- increases (contraction alkalosis)
Striated muscle in the GI tract
Pharynx, upper one-third of the espphagus and external anal sphincter
Respiratory alkalosis-muscle symptoms
Tingling, numbness, muscle spasm=
HYPOCALCEMIA
H+ and Ca2+ compete for binding sites on plasma proteins
Decreased [H+] –> ^ protein binding of Ca2+ and decreased free ionized Ca2+
Salicylate intoxication
-METABOLIC ACIDOSIS
salicylate acid , ^anion gap
-RESPIRATORY ALKALOSIS
Direct stimulation of medullary respiratory center
Parasympathetic innervation of the GI tract (parts)
Vagus: esophagus,stomach,pancreas,upper large intestine
Pelvic: lower large intestine,rectum,anus
Absorption of vitamins
FAT-SOLUBLE (A,D,E,K) :
incorporated into micelles and absorbed along with other lipids
WATER-SOLUBLE:
(most) by Na+ -dependent cotransport mechanisms
VITAMIN B12 :
requires intrinsic factor (secreted by parietal cells)
vitamin B12-intrinsic factor complex binds to a receptor in the ILEAL cells and is absorbed
“Official” GI hormones
Gastrin
Cholecystokinin (CCK)
Secretin
Glucose-dependent insulinotropic peptide (GIP)
Actions of gastrin
^ Gastric H+ secretion
Growth of gastric mucosa
“Official” GI hormones
Gastrin
Cholecystokinin (CCK)
Secretin
Glucose-dependent insulinotropic peptide (GIP)
Actions of gastrin
^ Gastric H+ secretion
Growth of gastric mucosa
Actions of CCK
1) contraction of the gallbladder/relaxation of the sphincter of Oddi
2) pancreatic enzyme secretion
3) potentiates secretin-induced stimulation of pancreatic HCO3- secretion
4) growth of the exocrine pancreas
5) inhibits gastric emptying!
Actions of secretin
1) pancreatic HCO3- secretion + growth of the exocrine pancreas
2) HCO3- and H2O secretion by the liver + bile production
3) INHIBITS H+ secretion by the parietal cells
Stimuli for the release of GIP
Fatty acids
Amino acids and
ORALLY administered glucose [—> oral glucose is more effective than intravenous glucose in causing insulin release]
GLP-1
binds to pancreatic β-cells and stimulates insulin secretion [analogues may be helpful in the treatment of type 2 diabetes mellitus]
Somatostatin actions
inhibits secretion of all GI hormones!!
+ inhibits gastric H+ secretion
Neurocrines of the GI tract
VIP (vasoactive intestinal peptide)
GRP (bombesin)
Enkephalins
Basis for the usefulness of the OPIATES in the treatment of diarrhea
Enkephalins inhibit intestinal secretion of fluid and electrolytes
Striated muscle in the GI tract
Pharynx, upper one-third of the esophagus and external anal sphincter
Interstitial cells of Cajal
pacemaker of the GI smooth muscle
produce slow waves
Slow waves (mechanism)
cyclic opening of the Ca2+ channels followed by opening of K+ channels
depol brings the membrane potential closer to threshold —>increases the probability that action potentials will occur
How to measure intrathoracic pressure
Using a balloon catheter placed in the esophagus
[lower than atmospheric]
Relaxation of the Lower Esophageal Sphincter- How
Vagally mediated and the neurotransmitter is VIP
When is gastric emptying inhibited/slowed?
1) when the stomach contents are hypertonic or hypotonic
2) fat (CCK)
3) H+ in the duodenum (direct neural reflexes)
Components of the gastrocolic reflex
- rapid parasympathetic component
- slower hormonal component mediated by CCK and gastrin
Mechanism of Protein absorption
LUMEN –> INTESTINAL CELL:
Na+ - dependent cotransport (amino acids)
H+ - dependent cotransport (di- and tripeptides)
INTESTINAL CELL –> BLOOD
Cytoplasmic peptidases hydrolyze di- and tripeptides to amino acids
All amino acids are transported by facilitated diffusion
Pancreatic secretions are …tonic
Always isotonic, regardless of flow rate
Hormones of the anterior lobe if the pituitary
1) Growth hormone
2) Prolactin
3) TSH
4) LH
5) FSH
6) ACTH
Which hormones are derived from POMC
ACTH
MSH (α- and β-)
β-lipotropin
β-endorphin
Regulation of ADH secretion
Increased by:
- ^ serum osmolarity
- volume contraction
- pain
- NAUSEA
- hypoglycemia
- nicotine, opiates, antineoplastic drugs
Decreased by:
- decr serum osmolarity
- ethanol
- α-agonists
- ANP
How hepatic failure affects thyroid hormones
TBG levels decrease –> decrease in total thyroid hormone levels but normal levels of free hormone
How pregnancy affects thyroid hormones
TBG levels increase –> increase in total thyroid hormone but normal levels of free hormone = clinically EUTHYROID
Thyroid hormones effect on Basic Metabolic Rate (BMR)
O2 consumption and BMR are increased in all tissues EXCEPT
brain
gonads and
spleen
due to increase of the synthesis of Na+,K+ ATPase
How does thyroid hormone have same actions as the sympathetic NS
up-regulates β1-adrenergic receptors in the heart
How glucocorticoids stimulate gluconeogenesis
1) ^ protein catabolism in muscle (and decrease protein synthesis) –> ^ amino acids provided to the liver for gluconeogenesis
2) decrease glucose utilization and insulin sensitivity of adipose tissue
3) ^ lipolysis –> ^ glycerol provided to the liver for gluconeogenesis
Anti-inflammatory effects of glucocorticoids (mechanism)
1) induce synthesis of LIPOCORTIN = (-) phospholipase A2 —> (-) liberation of arachidonate from membrane phospholipids —> (-) synthesis of prostaglandin and leukotriene
2) (-) production of IL-2 / proliferation of T lymphocytes
3) (-) release of histamine and serotonin from mast cells and platelets
Actions of glucocorticoids (in general)
1) Stimulation of gluconeogenesis
2) Anti-inflammatory effects
3) Suppression of the immune response
4) Maintenance of vascular responsiveness to catecholamines (up regulation of α1 - vasoconstriction)
Actions of mineralocorticoids
PRINCIPAL
- ^ renal Na+ reabsorption
- ^ renal K+ secretion
α-INTERCALATED
- ^ renal H+ secretion
Differences between Secondary adrenocortical insufficiency and Addison disease
Addison disease =primary adrenocortical insufficiency
Secondary adrenocortical insufficiency = primary deficiency of ACTH
DIFFERENCES:
In Secondary :
- NOT hyperpigmentation (because no ACTH)
- NOT volume contraction, hyperkalemia or metabolic acidosis (aldosterone levels are normal)
Hormone levels in 21β-Hydroxylase deficiency
Decrease in
cortisol and
aldosterone
(and gonadal hormones?)
Increase in ACTH adrenal androgens 17-hydroxyprogesterone and progesterone
Hormone levels in 17α-hydroxylase deficiency
Decrease in
androgen and
glucocorticoids
Increase in
mineralocorticoid and
ACTH
Why hypotension in diabetes mellitus
Result of ECF volume contraction.
high blood glucose –> high filtered load of glucose –> exceeds reabsorptive capacity (Tm) of the kidney –> unreabsorbed glucose acts as an osmotic diuretic
When does ovulation occur
14 days before menses REGARDLESS of cycle length
Basal body temperature during luteal phase
Increases because of the effect of progesterone on the hypothalamic thermoregulatory center
Major placental estrogen (second and third semester)
Estriol
Human Placental Lactogen
produced throughout pregnancy
actions similar to growth hormone and prolactin
Amine hormones
Thyroid, epinephrine , norepinephrine
= derivatives of tyrosine
Regulation of growth hormone secretion
Increased by
Sleep, stress, hormones related to puberty, starvation, exercise, hypoglycemia
Decreased by
Somatostatin, somatomedins, obesity, hyperglycemia, pregnancy
Prolactin excess
Results from:
- hypothalamic destruction
- prolactinoma
Causes:
- galactorrhea
- decreased libido
- failure to ovulate and amenorrhea
Treated with:
bromocriptine
Actions of ADH
1) ^ H2O permeability (aquaporin 2) on the principal cells of late distal tubule and collecting ducts (V2 receptor)
2) constriction of vascular smooth muscle cell (V1 receptor)
Why give oxytocin
- to induce labor
- to reduce postpartum bleeding
Iodide pump/Na+ - I- contrasporter is inhibited by
thiocyanate and perchlorate anions
Peroxidase in the follicular cell membrane is inhibited by
Propylthiouracil
—>used therapeutically to reduce thyroid hormone synthesis for the treatment of hyperthyroidism
Wolff-Chaikoff effect
High levels of I- inhibit organification —> inhibit synthesis of thyroid hormone
T3/T4 is more biologically active?
T3
Hormones that regulate prolactin secretion
Dopamine inhibits
TRH increases
Actions of ACTH
- Stimulates cholesterol desmolase –> (+) conversion of cholesterol to pregnenolone
- Up-regulates its own receptor at the adrenal cortex
- When chronically increased –> hypertrophy of the adrenal cortex
Actions of dexamethasone
Inhibits ACTH secretion (dexamethasone suppression test)
Dexamethasone suppression test
High or low dose and
measure CORTISOL levels
Regulation of aldosterone secretion
-tonic control by ACTH BUT -separately regulated by the renin-angiotensin system and -serum K+
Negative Ca2+ balance
=Intestinal Ca2+ absorption
Positive Ca2+ balance
Intestinal Ca2+ absorption > Ca2+ excretion
In growing children
The excess is deposited in the growing bones
How serum [Mg2+] affects PTH secretion
- Mild decreases in serum [Mg2+] stimulate PTH secretion
- Severe decreases in serum [Mg2+] inhibit PTH secretion —> symptoms of hypoparathyroidism (hypocalcemia)
How is resorption of the organic matrix of bone reflected
Increased hydroxyproline excretion
Urinary Ca2+ excretion in primary hyperparathyroidism
INCREASED because of the increased filtered load (exceeds Tm)
Chronic renal failure - Ca2+
1) decreased production of 1,25-dihydroxycholecalciferol contributes to decreased ionized [Ca2+]
2) decreased GFR –> decreased filtration of phosphate –> phosphate retention –> ^ serum [phosphate] –> complexes Ca2+ –> decreased ionized [Ca2+]
–> SECONDARY HYPERPARATHYROIDISM
Familial hypocalciuric hypercalcemia
Inactivating mutations of the Ca2+ -sensing receptors that regulate PTH secretion
Autosomal dominant
Decreased urinary Ca2+ excretion and ^serum Ca2+
Variation of FSH and LH levels over the life span
CHILDHOOD: hormone levels are lowest , FSH>LH
PUBERTY AND REPRODUCTIVE YEARS: hormone levels increase , LH>FSH
SENESCENCE: hormone levels are highest , FSH>LH
Levels of HCG during pregnancy
Peak levels at gestational week 9 and then decline
Estrogen production during the second and third semester
FETAL ADRENAL GLAND: dehydroepiandrosterone-sulfate (DHEA-S) –> hydroxylated in the FETAL LIVER –>PLACENTA: enzymes remove sulfate and aromatize to estrogens
[major placental estrogen: estriol]
Factors that decrease the duration of REM sleep
Benzodiazepines
Increasing age
At which phase of the cardiac cycle(+ECG) is the aortic pressure lowest
Just before the ventricle eject (between isovolumetric contraction and rapid ventricular ejection) -
After the QRS
Factors that may destroy the BBB
Inflammation
Irradiation
Tumors
Oxygen-hemoglobin dissociation curve in co poisoning
Shift to the left BUT also decrease in total O2-binding capacity —>decreased maximum percent saturation (max= 50%)
Where is estradiol synthesized
Testosterone is synthesized in ovarian theca cells and diffuses to ovarian granulosa cells where it is converted to estradiol by aromatase. FSH stimulates aromatase
How hypercalcemia affects the action of ADH
With severe hypercalcemia, Ca2+ accumulates in the inner medulla and papilla of the kidney
Diuretics and Ca2+
LOOP:
Ca2+ reabsorption is linked to Na+ reabsorption in the loop of Henle –> inhibiting Na+ with a loop diuretic also inhibits Ca2+ reabsoption—> loop diuretics increase Ca2+ excretion
—> treatment of hypercalcemia (volume to be replaced)
THIAZIDE:
increase Ca2+ reabsporption in the early distal tubule –>
decrease Ca2+ excretion
—> treatment of idiopathic hypercalciuria
How ^ intracellular Ca2+ excitates smooth muscle cell
binds to calmodulin
Difference between action potential of a ventricular muscle cell and an atrial muscle cell
atrial muscle cells have a much shorter plateau phase and a much shorter overall duration
Causes of nephrogenic diabetes insipidus
- Lithium intoxication: inhibits the Gs protein in collecting duct cells
- Hypercalcemia: inhibits adenylate cyclase
Diuretics and Ca2+
LOOP:
Ca2+ reabsorption is linked to Na+ reabsorption in the loop of Henle –> inhibiting Na+ with a loop diuretic also inhibits Ca2+ reabsoption—> loop diuretics increase Ca2+ excretion
—> treatment of hypercalcemia (volume to be replaced)
THIAZIDE:
increase Ca2+ reabsporption in the early distal tubule so that urinary Na+ excretion is increased –>
decrease Ca2+ excretion
—> treatment of idiopathic hypercalciuria
COPD causes ….ventilation
hypoventilation
K+ in vomiting
Hypokalemia because
- loss of gastric K+
- ^aldosterone due to volume contraction
No p waves and bizarre QRS complexes
Where did they originate
NOT SA node (no p)
NOT AV node (bizarre and not normal QRS)
NOT VENTRICULAR MUSCLE (no pacemaker activity)
!His-Purkinje system yes (pacemaker activity but not normal QRS)
Metabolic acidosis + decreased urinary excretion of NH4+ =
Chromic renal failure
Which GI hormones are secreted by cell of the duodenum
Secretin and CCK
