KICK THE BOARDS

USMLE STEP 1
Physi ology



Pr epar ed by
Dr . Ir f an Mir



KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
1


C ELL PHISIO LO G Y
* Cell mem composed of phospholipids bilayer which contain glycerol back bone.
* Glycerol back bone composed of head (hydrophilic) and two fatty acid tails (hydrophobic). Tails face each other.
* Lipid soluble substance cross cell mem whereas water soluble pass through channel, pores and carriers.
* Inte g ra l p rote in span the entire mem (eg. Ion channel) whereas, peripheral protein located either inter or extra
cellular side.
* Tig ht Junc tion ( zona oc c lud e s) ------- are attachment b/ w cells serve intracellular pathway for solute. It may be tight
(Impermeable) as in renal distal tubules or leaky (permeable) as in renal proximal tubule or gall bladder.
* G a p junc tion -- is attachment b/ w cells which permit IC communication eg. In myocardial cells.
* Simp le d iffusion -- is the transport which is not carrier mediated. It occur down an electrochemical gradient does
not require energy passive.
Diffusion can be measured by J = - PA (C1 - C2) (J= flow, P= permeability, A= area, C= conc entra tion)
* C a rrie r me d ia te d tra nsp ort shows ste re osp e c ific ity, sa tura tion a nd c omp e tition.
Stereospecificty means D-glucose (natural isomer) can transported where as L-glucose (L-isomer) can not.
Saturation means transport | as the concentration | until carriers are saturated called Tm (transport maximum)
Competition means structurally related solute compete for transport site.
eg. (Galac tose is competitive inhibitor of glucose in small Intestine).
* Fa c ilita te d d iffusion -- occur down an electrochemical gradient, does not require energy is passive. It is carrier
Mediated and more rapid than simple diffusion.
* Prima ry Ac tive tra nsp ort -- occur against the electrochemical gradient (up hill). It utilize metabolic energy (from
terminal bond of ATP) is active. It is also carrier mediated ( exhibit stereospecificity, sa tura tion and competition) .
Eg. Na+ - K+ ATPase (usual st oichiomet ry is 3Na / 2K) ,Ca++ ATPase in sarc oplasmic reticulum, K+ - H+ ATPase in parietal cells.
* Se c ond a ry Ac tive tra nsp ort -- in which transport of two or more solute is coupled. One of the solute is transported
down hill (usually Na+) which provide energy for uphill transport of other solute. Metabolic energy provided
indirectly from Na gradient. Thus the inhibition of Na+ - K+ ATPase results into inhibition of Secondary transport.
Eg. Na+ - glucose Cotransport in renal proximal tubule, Ca++ - Na+ exchange, Na+ - H+ exchange. Poisoning the
Na+ - K+ pump eventually results into inhibition of Ca++ - Na+ exchange due Na+ imbalance across cell mem.
* Cotra nsp ort or symp ort is transport of solute in the same direction whereas, C ounte r tra nsp ort or a ntip ort or
e xc ha ng e is the transport of two solute in opposite direction to each other.
* O smola rity is the conc (C) of osmotically active particle in a solution. Osmolarity = g × C (g is no of p artic le in the solu.
* Solution with high osmolarity is hyperosmotic, low osmolarity is hypoosmotic, and same osmolarity is isosmotic.
* O smotic Pre ssure (van’ t Hoff’ s Law) depends on the conc of osmotic particles. | in solute particle results in |
osmotic P. It can be measured by t = g × RT× C (Where R is gas constant 0.082L - atom/ mol - °K. and Tis
absolute temp °K).
* Re fle c tion c oe ffic ie nt is the no b/ w zero & one. It explains the ease with which solutes permeate the mem. If
Reflection coefficient is 1 the solute is impermeable & when it is zero solute is permeable. eg. Reflection coefficient
of albumin (big solute) is 1 where as urea (small solute) is zero.
* Ion c ha nne ls are open or closed by gates.
It may be volta ge g a te d channel which open or closed by change in mem potential. Eg Na channel in nerve
action potential. It may be Lig a nd ( c he mic a l) g a te d channel which open or closed by hormones, second
messenger, neurotransmitters.
* Diffusion p ote ntia l is the potential difference generated across a mem because of conc difference of an ion.
* Eq uilib rium p ote ntia l is the diffusion potential which exactly balance (opposes) the tendency for diffusion caused by
conc difference. There is no more net movement because electrical driving forces on ion are equal and opposite..
* Ne rnst e q ua tion is used to calculate equilibrium potentials. E = -2.3 RT log10 [Ci]
zF [Ce]
E Na+ is + 65mV
E Ca++ is + 120Mv
E K+ is - 85mV
E Cl- is - 90mV
* Re sting me m Pote ntia l is the measured potential difference in mV (millivolts), it is established by diffusion potential.
The resting mem potential of nerve is -70 mV. At rest nerve mem is far more permeable to K+ than to Na+ at rest.
* Thre shold is the mem potential at which occurrence of action potential is inevitable. Inward current depolarize the
mem to Threshold.
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
2


* Upstroke of action potential is depolarization cause rapid opening of the activation gates of Na+ channel. Na
enters into the cell.
* De pola riza tion also open K+ gates and closes the Na+ channel gates but at slower rate. This combined effect make
K+ conductance higher than Na+ conductance in last quarter of depolarization which make mem potential to
Repolarize.
* Re pola riza tion is caused by outward K+ current.
* O ve r shoot is the portion of action potential when mem potential is positive whereas Und e r shoot ( hyp e rp ola riza tion)
makes the mem potential more negative (c lose to K+ equilibrium potential).
* Ab solute ly Re fra c tory p e riod is the period during which another action potential cannot be elicited no matter how
large the stimulus is.
* Re la tive re fra c tory pe riod begins at the end of absolute refractory period and continuous till mem potential return
to its resting potential. Stronger than usual current can elicit the action potential.
* | Fiber size and myelination can | the conduction velocity of action potential. Remember myelinated nerve exhibit
saltatory conduction because action potential can be generated only at the Node of Ranvier.
* End Pla te p ote ntia l (EPP) in the postsynaptic mem is not an action potential but a depolarization of specialized
muscle end plate. Once the end plate region is depolarized local current cause depolarization and action
potential in the adjacent muscle.
* Excitatory postsynaptical potential (EPSP) bring the cell closer to fire action potential where as Inhibitory
Postsynaptical potential (IPSP) hyperpolarize the postsynaptical cell by opening Cl- channels..
* Thick filament contain myosin present at A band. vs. Thin filament contain actin, tropomyosin & troponin present
at I band.
* Myosin head bind ATP and actin and are involved in cross bridging formation.
* Ttubule are present at the junction of A band and I band. It carry depolarization to the interior of the cell.
* Ske le ta l musc le c ontra c tion -- sarcoplasmic reticulum (SR) are internal tubular structure site of Ca++ storage and
release. Ca bound loosely to calsequestrin with in SR & it release upon depolarization bring by Ttubules. Released
Ca+ bind to troponin C on the thin filament causing conformational change in Troponin (which is tropomyosin
moving out of way so that cross bridge cycle can begin). Actin myosin binds and filament slide over each other and
ATP is hydrolysed.
* Le ngth Te nsion re la tionship :-
1. Pa ssive te nsion -- is tension developed by stretching to Fixed length (preload).
2. Tota l Te nsion -- is tension developed when the muscle is stimulated to contract at different length.
3. Ac tive Te nsion -- is the difference b/ w total tension and passive tension.
* Smooth musc le c ontra c tion -- smooth muscle has thick & thin filament & are not arranged in sarcomere. (vs. stria ted m)
There is no troponin instead Ca++ regulate myosin on thick filament Ca++ enter in the cell across cell mem it may
cause release of additional Ca++ from SR via Ca++ - gated channels. Hormones and neurotransmitters also release
Ca++ from SR through IP3 gated Ca++ channels. IC Ca++ |. Ca++ bind to Calmodulin and Ca++ - calmodulin
complex bind to and activate myosin light chain kinase which further phosphorylate myosin and allow it bind with
actin. Contraction follow.
* Dephosphorylation of myosin cause relaxation where as in striated muscle Ca++ uptake cause relaxation.
Remember in heart and striated muscle Ca binds with troponin and in smooth muscle Ca binds with calmodulin.

Figs:












KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
3


ENO DC RO NO LO G Y
* * SEC O ND M ESSENGER SYSTEM :-
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
C YC LIC AM P I P3 C a ++ STERO I DS TYRO SI NE KI NASE C YC LIC G M P
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
CRH GnRH Minera lcorticoids Insulin ANF
ACTH TRH Glucocorticoids IGF EDRF (NO)
TSH GHRH Estrogen
PTH ADH ( V1 ) Progesterone
ADH ( V2 ) Oxitocin Testosterone
|1, |2, o2 o1 Vit D
FSH, LH Angiotensin II T3, T4
HCG CCK
M2 M1 , M3
MSH GABA
Calcitonin
Gluca gon
Secretin
Dopamine
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* TSH, FSH, LH, HC G are the member of same glycoprotein  bears o sub unit (identical) & | sub unit (unique for hormone).
* ACTH, M SH, | Lip otrop hin, | End orp hin, all derived from POM C .
* o MSH, and | MSH Rudimentary in adult.
* G HRH  G H ( a c idop hillic sta in) .
Functions :- * + Glucose uptake ( Diabetogenic )
* | lipolysis
* | Protein Synthesis ( | LBM )
* | Production of IGF (insulin like growth factor)
* Soma tosta tins and Soma tome d ins have imp negative feed back function.
* Somatostatin block GHRH effect on AP. vs.
Somatomedins cause +ve feedback on the release somatostatin from HT
--------------------------------------------------------------------------------------------

* PL ( a c id op hilic to c hromop hob ic sta in) . PL se c re tion | b y TRH and inhib it b y Dop a mine .
Func tion:-* Lactogenesis
* Breast development
* Inhibit Ovulation ( via + Syn of GnRH ) * inhibit spermatogenesis (via + GnRH)
Pa tholog y :- * Failure to lactate
* Failure to ovulate
* Galactorrhea (hypothyroidism can cause increase in TRH with resultant gala c torrhea)
--------------------------------------------------------------------------------------------

* ADH originate in supraoptic nuclei of hypothalamus ( Post lobe ). Act on receptors V1 ( vasoconstriction ) and
V2 ( | distal tubule and collecting duct permeability)
* O xitoc in originate in paraventricular nuclei of hypothalamus ( post lobe ). Major stimulus for secretion is Suckling,
sight and sound of infant.
* Ne urop hysin is CNScarrier protein for both hormone (ADH, Oxitocin).

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* C a use s of | or + se c re tion o f ADH :: | Se c re tion o f ADH vs. + se c re tion of ADH
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
* | se rum osmola rity * + se rum osm o la rity
* V o l c ontra c tion * Etha nol
* Pa in, Na use a ( strong ) * o Ag onist
* Hy p og lyc e mia * ANP
* Ne c otinic op ia te
* Antine op la stic d rug
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
4


* Func tion of Oxitoc in : Myoepithelial contraction of mammary gland, Milk ejection, Contraction of uterus, Dilatation
of Cervix and Orgasm. ( it can be used to induce labour ).
* TRH  TSH  T3, T4 ( stored in lumen). ( Ba sop hilic a nd c hromop hob ic sta in)
* Iodide pump ( I - ) present in thyroid follicular epithelial cell.
* Iodide pump Inhibit by Thiocyanate and Perchlorate ion.
* T3, T4 syn can be inhibited by | dosis of Iodine ( I 2 ) this is called Wolf Charkoff Effect.
* T3 is 4 times more potent than T4.
* Thre e sta ge s of TH syn :- 1. O xid a tion :- 2 I - ( Iodide )  I2 ( iodine ) --------- ( Propylthiouracil inhibit oxidation).
2. O rg a nific a tion :- I2 + Tyrosine of Thymoglobulin  MIT + DIT
3. Coup ling re a c tion :- MIT + DIT  Triidothyroxine T3 ( active form )
DIT + DIT  Thyroxine T4
* Befor release Iodinated thyroglobulin first must be taken back into the follicular cell from lumen for digestion of
thymoglobulin by lysosoma l e nz to release T3 T4. ( left over MITand DITare digested by thyroid de iod ina se ).
* T3 T4 circulate by Thyroid Bind ing G lob ulin.
* Conversion of T4 into T3 ( a c tive form) and Re ve rse T3 ( ina c tive form) take place in target tissue by enz Iod ina se .
* Enz 1,5 monod e iod ina se cause break down of T3 and Reverse T3, its deficiency results into | T3 and Reverse T3.
* Func tion of thyroid hormone :-
1. Growth, Bone formation, and maturation.
2. CNS-- Prenatal CNSmaturation
In Adults ---- Hyp e rthyroid ism ( Grave’ s dis, Plummers $ )  Hyperexcitability, Irritation. Palpitation etc.
Hyp othyroid ism ( Myxedema, Cretinism, Hashimoto thyroiditis, De Quervian thyroiditis, Reidal
thyroiditis )  + mental capacity, impaired memory, slow speech,
listlessness, Somnolence, etc.
3. Autonomic nervous sys :- | Adrenergic Stimulation.
4. BMR :- | O2 consumption and BMR except in Spleen, Gonad and Brain (results into | body temp).
| Syn of Na+ K+ ATPase (results into | O2 consumption)
| HR, | Ventilation (ensure more O2 delivery to tissue)
5. Metabolic effect are over all catabolic .
* Grave dis in which IgG ( thyroid stimulating imunoglobin)  | T3, T4

--------------------------------------------------------------------------------------------------------------------------
* PTH is secreted by C hie f c e lls and regulate serum Ca++.
* 1,25 Dihyd roc hole c a lc ife rol is active form of Vitamin D, produce by 1o hyd oxyla se in kidney to Provide C a ++ &
Phosp ha te for normal bone mineralization.
* C a lc itonin Syn and secreted by Pa ra follic ula r c e ll ( C.c e lls ) of thyroid. Its major action is to inhib it b one Re sorption.

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
PTH VIT D C ALC ITO NI N
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Stimulus for se c re tion:- + Serum Ca++ + Serum Ca++ * | Serum Ca ++
Mild + in serum Mg + Serum Phospha t Severe + serum Mg inhibit secretion. | PTH

Ac tion on Bone :- | Resorp tion | Resorption * + Reabsorption

Ac tion on Kid ne y :- | Ca++ Reabsorption | Ca++ Reabsorption
+ Ph Reabsorption | Ph Reabsorption

Ac tion on Inte stine :- | Ca++ Absorp tion (via Vit D) | Ca++ Absorp tion (via vit D Ca++ binding Protein)

O ve ra ll e ffe c t :- Serum Ca++ | Serum Ca++ | * Serum Ca++ +
Serum Ph + Serum Ph |
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* Resorption of organic matrix of the bone is reflects in | Hyd roxyp roline Exc re tion.
* PTH | Ca++ reabsorption at distal tubule where as in proximal tubule PTH | inhibit Ph reabsorption with resultant
excretion of nephrogenous cyclic AMP.
* PTH | Vit D production ( indirectly ) by stimulating 1 o Hyd roxyla se .
* Vit D mineralize new bone by | Ca++ and Ph in serum.
* Hyp op a ra thyroid ism  Tetany ( + Ca++, | Ph ).
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
5


* Hyp e rp a ra thyroid ism  |Ca++,+ serum Ph,| phosphaturia,| Urinary cAMP, | Bone resorption ( with resultant | in
calcitonin & Vit D).
* Pse ud ohyp op a ra thyroid ism ( Alb rig ht he re d ita ry O ste od ystrop hy ) is due to defective G Protein in target tissue with
resultant resistance to PTH which cause | PTH, + Ca++, | Ph.
* Vit D De fic ie nc y  Osteomalacia and Rickets .

Diet ÷ cholecalceferol ÷ 7 Dehydrocholecalciferol ( In skin through ultra voilet light )
+
25.OH. Choleca lciferol ( In Liver )
+
Kidney
.\ ÷ ( 1 o Hydroxylase ) © ÷ ( |PTH, +Ca++, +Ph )
1,25 hydrocholecalciferol 24,25 (OH)2 Choleca lciferol

* Remember | PTH, + Ca++, and + Ph have positive stimulating effect on enzyme 1o Hydroxylase hence ↑ it activity.

-------------------------------------------------------------------------------------------------------
* Zona G -- Mineralcorticoids (Aldosterone)
Zona F -- Glucocorticoids (Corticosteroids)
Zona R -- Androgen (Testosterone, Estradiol)

** Cholesterol
+ 17 o Hydroxylase 17 . 20 Lyase
Pregnenolone ÷ 17 Hydroxypregnenolone ÷ Dehydroxyandrosterone

+ 3 | hydroxysteroid Dehydrogenase + 3 | hydroxysteroid dehydrogenase + 3 | hydroxysteroid dehydrogenase
Progesterone ÷ Hydroxyprogesterone ÷ Androstenidione
17, 20 lyase 17| Osteroid dehydrogenase
+ 21 | hydroxylase 21 | hydroxylase + + and Aoma ta se
11 Deoxycorticosterone 11 Deoxycortisol Testosterone / Estradiol

+11| Hydroxylase + 11| Hydroxylase
corticosterone Cortisol

ATII & ↑K+ ÷ © + Aldosterone synthase
Aldosterone .

* G luc oc ortic oid s :- CRH (from paraventricular nuclei) ÷ ACTH (AP) . (Both synthesize by POMC).
Release in circardian rhythm, Cortisol | at 6 AM and + at 12 midnight.
* ACTH up regulate its own receptor. Cortisol cause -ve feed back inhibition to both CRH and ACTH.
* Glucocorticoids are essential in response to stress. | cortisol level cause bone resorption.

* G luc oc ortic oid Func tions :- 1. Gluconeogenesis :- | protein catabolism and + protein syn.
| lipolysis
+ glucose utilization (hyperglycemic)
2. Anti inflammatory :- syn of lipocortin
inhibit phospholipase A2
inhibit IL2 ( so inhibit T.cell proliferation )
inhibit histamine and serotonin.
3. Maintain vascular responsiveness to catecholamine.

* M ine ra lc ortic oid s :-
* Hypovolemia ÷ | Renin ÷ ATI ÷ ATII ÷ | Aldosterone ÷ | Na + re a b sorp tion, | K+ se c re tion, | H+ se c re tion.
* Hyp e rka le mia cause | Aldosterone secretion.
* And roge ns :- Androstenidione produce Testosterone in testes and Estraidol in ovary.
+ Deficiency of 17, 20 lyase ÷ Ab se nc e of And rog e n.
+ Deficiency of 3 | hydroxysteroid dehydrogenase ÷ Ab se nc e of e ve ry thing .
+ Deficiency of 21 | hydroxylase ÷ Ab se nc e of G luc oc ortic oid s a nd M ine ra lc ortic oid s.
+ Def of 11 | hydroxylase ÷ Ab se nc e of Cortisol only ( b e c a use 11- d e oxyc ortic oste rone ha s p a rtia l Ald oste ro ne a c tivity 3% )
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
6


* Pa tholog y :- 1. Ad re noc ortic a l Insuffic ie nc y ( Ad ison d is) .
+Prima ry - Commonly cause by autoimmune destruction of Adrenal cortex.
- + glucocorticoids, mineralcorticoids and androgen ÷ | POMC, | ACTH.
- Hypoglycemia, hyperpigmentation, vol contraction, hyperkalemia, metabolic acidosis Aldosterone def.
+Se c ond a ry - Caused by + ACTH .
- Does not exhibit vol contraction, hyperkalemia, metabolic acidosis because aldosterone is normal.
2. Ad re noc ortic a l Exc e ss . | cortica l & androgen level, hyperglyc emia, muscle wasting, c entral ob esity, moon fac e buffa lo hump,
suprac lavicular fa t, poor wound healing, striae, hypertension, osteoprosis, virilization of fema le.
+ C ushing $ ÷ commonly cause by Glucocorticoid therapy and adrenal gland hyperplasia.
+ C ushing Dis ÷ Overproduction of ACTH.
3. Hype ra ld oste ronism (Conn $) -- cause by tumor.( hyp ertension, hypokalemia, metabolic a lkalosis, + renin secretion )
4. Wa te r house Frid e ric hson $ :- Catastrophic adrenal insufficienc y due to hemorrhagic necrosis of adrenal c ortex often because
of Meningococca l meningitis.
5. Ad re nog e nita l $ :- 21 | hyd roxyla se d e fic ie nc y -- - + Cortisol and Aldosterone.
- | Hydroxyprogesterone and progesterone.
- | ACTH ÷ hyperplasia of Zona F and Zona R .
- | Adrenal androgen.
- Virilization of female (early linear growth, pubic and axillary hair).
- suppress gonads function in both sexes.
--------------------------------------------------------------------------------

* End oc rine Pa nc re a se :- o cells ---- O ute r c e ll isle t ---- Glucagon
| cells ---- C e ntra l isle t ---- Insulin
o cells ---- Inte rmix ---- Somatostatin, Gastrin.
+ Pa nc re a tic polyp e p tid e :-
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
v Insulin ( Tyrosine kina se re c e p tor) stimula tion for se c re tion O ve r a ll Effe c t
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
| blood glucose + blood glucose
| AA
| Fa tty a cid
Glucagon
GIP ---------------------------------------------- + AA
GH ---------------------------------------------- + Fa tty a cid
hypokalemic ÷ Cortisol ---------------------------------------- + Ketoa cid
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
v G luc a g ons ( c AM P me c h ) Stimula tion for se c re tion O ve r a ll Effe c t
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
+ Blood glucose | Blood glucose
| AA
CCK ---------------------------------------------- | Fa tty acid
EN, Nor EN, Ac h ------------------------------- | Ketoacid ( | Hydroxubutyra te and a cetoaceta te )
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* G luc a g on act only on liver ÷ Glycogen break down.
Glucagon ÷ + Fruc tose 2,6 Bip hosp ha te p roduc tion a nd + Phosp hofruc tokina se a c tivity.
( Tha t's why also cause gluconeogenesis, in addition to Glycogenolysis, Lipolysis, and Ketone produc tion).
* Insulin consist of o subunit and | subunit among which | subunit have tyrosine kinase activity.
* Insulin d own re g ula te s its own re c e ptor. Receptor | in starvation and + in obesity.
Ac tion :- | uptake of glucose and promote glycogen formation.
Inhibit Glycogenolysis and + Gluconeogenesis.
Decreases Fatty acid , ketones, AA, and serum K+ concentration
Inhibit lipolysis and stimulate fat deposition.
* Insulin def → into hypokalemia, hypotension and noc turia. Also ketosis which results into metabolic acidosis  compensa tory hyp erventila tion.
* Soma tosta tin :- Inhibit secretion of Glucagon, Insulin, Gastrin, and Intestinal absorption of Glucose.
* insulin secretion is media ted by ca++ channel op ening in | c ell. + Blood glucose, soma tosta tin and EN, Nor EN + insulin secretion.


KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
7


* Te stoste rone synthesize by 5 o reductase and secreted by Leydig cells.

Cholesterol d esmolase
Cholesterol ÷÷÷÷÷÷ Pregnenolone
| © +
LH 17 hydroxypregnenolone
+
Dehydroxyandrosterone
+
Androstenidione
17 | OH steroid Dehydrogenase +
Testosterone
5 o reduc tase +
Dihydrotestosterone (ac tive form)


( Inhib in re le a se from se rtoli c e lls, it c a use - ve fe e d b a c k a ffe c t on the re le a se of FSH from Ant p ituita ry )
* G nRH originate from arcuate nuclei of hypothalamus & secrete in pulsatile manner.
G nRH up re g ula te its own re c e ptor in AP.
Te stoste rone Ac tion :- * Prenatal differentiation of wolfian duct and external genitalia.
* Develop male Secondary sexual characteristics at puberty.
* Cause pubertal growth spurt.
* Maintain spermatogenesis (by paracrine effect of testosterone) and increases libido.
* | Size and secretory activity of epididymus, Vasdefrens, prostate and seminal vesicle.
* 5 o reductase inhibit by Finastride it can be used in BPH.
-----------------------------------------------------------------------------------------

* ESTRO G EN AND PRO G ESTERONE :-
HT ÷ GnRH ÷ AP
* FSH a nd LH  Cause Steroidogenesis in ovarian follicle & corpus luteum. .\
Follicular development beyond the antral stage. LH FSH
Ovulation + +
Leutinization Theca c ell Granulosa c ell
+ + aroma tase
Testosterone ( Androgen ) Estrogen
(convert And rogen into estrogen)

LH © FSH ©
Cholesterol ÷ Pregnenolone ÷ 17 Hydropregnenolone ÷ dehydroepiandrosterone ÷ androstenidione ÷ testosterone
(theca cell) ↓ Aroma tase
17| estradiol. (granulosa c ells)

* Aromatase convert testosterone into 17| Estradiol.
* In male FSH cause sp erma togenesis in sertoli cell where as in fema le it cause 17| Estradiol synthesis in granulose c ell.
* In male LH hormone ca use testosterone synthesis in leydig cells where as in fema le it cause testosterone synthesis in theca c ells.
* Estrog e n Func tion :-
1. - ve and + ve feed back effect on FSH and LH secretion. ( where as progesterone cause - ve feed back )
2. Maintainance and Maturation of fallopian tube, uterus, cervix, and vagina.
3. Development of female sec sexual characterstics.
4. Development of breast.
5. Upregulate estrogen, LH, and progesterone Receptor.
6. Development and proliferation of granulose cell.
7. Maintain pregnancy.
8. Lower uterine threshold to contractile stimuli during pregnancy vs.(progesterone Raise uterine threshold to contrac tile stimuli
during pregnancy)
9. Stimulate PL secretion but block its action on breast.
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
8


* Proge ste rone Func tion :-
1. - ve feed back effect on FSH, LH. ( where as estrogen cause both - ve and + ve feed back )
2. Maintain secretory activity of uterus in luteal phase.
3. Maintain pregnancy.
4. Raise uterine threshold to contractile stimuli during pregnancy vs.
Estrogen Lower uterine threshold to contractile stimuli during pregnancy.
5. Responsible of development of breast.

 + ve & - ve FEED BAC K C O NTRO L O F M ENSTRUAL C YC LE.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Pha se of C yc le Horm one Ty p e of Fe e d Ba c k Site
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Follicular Phase Estrogen - ve AP
Mid Cycle Estrogen + ve AP (ovula tion occur)
Lutea l Phase Estrogen - ve AP
Progesterone - ve HT
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Fig:



















* M e nstrua l c yc le :-
1. Follic ula r p ha se ( d a y 5 - 14) :- In which Primodial follicular development and uterus proliferate.
Estradiol | steadily and FSH, LH suppressed And Progesterone is low.

2. Ovula tion ( d a y 15) :- Occur 15 days prior to menses regardless of cycle length.
Estradiol ÷ + ve feed back on FSH, LH ( re sponsib le for LH surg e ) .
Ovulation occur as a result of estrogen induced LH surge.
Estrogen + just after ovulation and | again in leuteal phase ( sourc e of this | is c orp us le ute um)
Cervical mucous | and become less viscous.

3. Le ute a l Pha se ( d a y15 - 28) :- Corpus leuteum develop and syn of estrogen and progesterone occur from it.
| vascularity and secretory activity of endometrium..
Basal body temp | (progesterone act on HTthermoregulatory center)
If fertilization not occur corpus leuteum regresses ÷ + Estradiol and Progesterone.
If fertilization occur Estradiol and progesterone keep | steadily.
4. M e nse s ( d a y 1 - 4):- Is sloughing of endometrium because of with drawal of Estradiol and progesterone.
----------------------------------------------------------------------------------------

KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
9


* PREG NANC Y :-













* 1
ST
TRIMESTER :- HCG stimulates corpus leuteum to produce Estradiol and progesterone.
HCG peak occur at week 9 and than it declines.

* 2
nd
& 3
rd
TRIMESTER : Progesterone produce by placenta & estrogen produce by fetal adrenal gland & placental
Interplay. Major Placental Estrogen is Estriol.
HPL (Human Placental Lactogen).has GH and PL like effect produce through out pregnancy

* PARTURITION :- Initiating event is unknown. (there is no change of blood oxitocin level prior to labor even though it is
potent stimulator of uterine contraction)
* LACTATIO N :- PL | steadily during pregnancy but estrogen and progesterone block the action of PL on breast.
After parturition estrogen and progesterone + and lactation occur.
Ovulation is suppressed by PL because PL inhibit GnRH secretion from HTwith resultant + in FSH and LH.
PL also antagonise the action of FSH and LH on ovaries.
Suckling stimulates both oxitocin and PL secretion.
---------------------------------------------------------------------------------------------

G I PHYSIO LO G Y
* STRUC TURE AND INNERVATIO N :
Epithelial cell may be secretive or absorptive.
M usc ula ris muc osa --- contraction cause change in surface area.
C irc ula r musc le --- contraction cause decrease in diameter of the lumen.
Long itud ina l musc le --- contraction cause shortening of GI segment.
Sub muc osa l p le xus a nd M ye nte ric p le xus -- is enteric nervous sys which integrate and coordinate the motility,
secretion and
Endocrine function of GI tract.
Fig:










* INNERVATIO N O F G I TRAC T :- consist of extrinsic nervous sys and intrinsic nervous sys.
Extrinsic ne rvous sys:- Comprise of Sympathetic and Parasympathetic nervous sys.
Parasym is Excitatory via vagus & pelvic nerves where as sym is inhibiting originate from T8 - L2.
( Vagus supplies to esophagus , stomach, pancreas & upper large intestine where as p elvic supp lies to lower large intestine, rec tum and anus )
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
10


Preganglionic cholinergic fiber synapse in prevertebral ganglion.
Post ganglion adrenergic fiber synapse in submucosal and myenteric plexus.
Some direct post ganglionic adrenergic innervation to blood vessel & smooth muscle also
occur here.
Intrinsic ne rvous sys:- Intrinsic sys relay information to and from GI to CNS.
Intrinsic sys also relay information with in GI by local reflexes.
Myenteric plexus (Auerbac h,s plexus) control motility of smooth muscle
Submucosal plexus (Meissner,s plexus) receive sensory information from chemo and mechano
receptor and control secretion and blood flow.
* G I HO RM O NES :-
Hormone s ( only 4) ---------- Gastrin , CCK, Secretin, GIP --- It enter portal and sys circulation and act on distal sites.
Pa ra c rine ( only 2) ----------- Somatostatin and Histamine --- Release from GI cells and act on short distance.
Ne uroc rine ( only 3) - - - - - - - VIP(vosotive intestinal peptide), Gastrin releasing peptide (Bomb esin), Enkephalin (met E, leu E)
Neurocrine synthesize in neuronal body move down by axons & release by nerve action potential.

* Gastrin ---- Little gastrin have 17 AA. Big gastrin have 34 AA (it is not a dimer of little gastrin).
Gastrin’ s 4 C terminal AA contain biologic activity.
Gastrin is a potent H+ releaser than histamine.
CCK also has gastrin like activity .
* Secretin --- all AA require for biologic activity.


----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Horm one s Homolog y Site of se c re tion Stimulus for se c re tion Ac tion
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Gastrin CCK G Cell (stoma ch) Sma ll p ep tide, AA specially | gastric H+ secretion.
Phenylalanine and Tryp tophan stimula te growth of gastric mucosa.
are potent stimula ter. (prietal c ell, mucosa of intestine & colon)
Distention of stoma ch .
Vagus via GRP.(a tropin does not inhibit Gastrin release b ecause
mediator of gastrin release is GRP not Ach)
Inhibit by H+ in stomach via Soma tosta tin.

CCK Gastrin I cell of Small p eptide a nd AA. Contra c tion of gallbladd er & relax sphinc ter of oddi.
(33AA) doud enum & fa tty a cid. Secrete pancrea tic enz.
Jejunum monoglyc erides. Secrete pancrea tic HCO3 via secretin.
(but not triglycerid es) Growth of endocrine pancrease & gall bladder mucosa.
Inhibit gastric emp tying.

Secretin Glucagon Scell doudenum H+ and fa tty acid in Doud enum Stimula te pancrea tic HCO3 and H2O secretion.
Stimula te biliary HCO3 secretion.
| growth of exocrine pancrease.
Inhibit H+ secretion.
Inhibit gastrin on growth of gastric mucosa.
(Gastric Inhibitory p ep tide)
GIP Secretin Doud enum and Fa tty ac id, AA, & Ora lly ad ministered Stimula te insulin release.
Glucagon jejunum Glucose. Inhibit H+ secretion.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* G I p a ra c rine : Soma tosta tin -- Secreted in response to H+ through out GIT, & its secretion is inhibited by vagus nerve.
Somatostatin inhibits all GI hormone and gastric H+ secretion
Hista mine ------- Secrete by mast cell induce gastric H+ secretion
Histamine also potentiate its effect on Ach and gastrin ÷ | H+ secretion.
* G I ne uroc rine s: VIP Cause GI smooth muscle relaxation, stimulate pancreatic HCO3 secretion & inhibit Gastric H+
secretion. VIP producing pancreatic tumor of islet cell ÷ pancreatic cholera
G RP (bombesin) -- release from nerve ending by vagal stimulation ÷ stimulate Gastrin release.
Enke p hlins -- Contract GI smooth muscle of lower esophageal, pyloric, and iliocecal sphincter.
Enkephlins also inhibit intestinal secretion of fluid and electrolytes.

KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
11


* G I M OTILITY :- Contractile tissue of GITis unitary smooth muscle except pharynx, upper 1/ 3 of esophagus and
external anal sphincter which are straited muscle.
Pha sic Contra c tion ---- contraction and relaxation found periodically in esophagus, antrum and intestine.
Tonic c ontra c tion ------- found in lower esophagus sphincter, orad stomach, iliocecal and internal anal sphincter.
* Slow wa ve are osc illa ting me m pote ntia l which is essential to smooth muscle.
* Slow wave are not action potential but they do determine the pattern of action potential and contraction.
* Depolarization of slow wave bring mem potential closer to threshold to initiate action potential.
* Frequency of slow wave not influence by neuronal or hormonal input where as action potential yes.
* Frequency of slow wave lowest in stomach (3/ min) and highest in doudenum (12/ min).

* SALIVA :- There are 3 major glands, Parotid, maxillary and sublingual gland.(myoepithelial a nd duc ta l cells contrac t to ejec t
saliva in mouth)
* At lowest flow rate saliva has lowest osmolarity & | K+ conc vs.
At highest flow rate saliva has osmolarity close to plasma.
* The Acinus produce initial saliva whose composition is same as plasma but duct modify the saliva by reabsorbing
Na+ and cl- and secreting K+ and HCO3.( Aldosterone ac t on duc tal c ell ÷ | reabsorp tion of Na+ and secret K+ )
* Duct is relatively impermeable to water ÷ hypotonic saliva
* Parasympa thetic stimula tion is through facia l nerve VII and glossopharyngeal nerve IX ÷ | produc tion of sa liva (rec ep tors are muscarinic and
2
nd
messenger is IP3 where as sympa thetic stimula tion also cause | produc tion of saliva but rec ep tors are | and 2
nd
messenger is c AMP.

* SWALLO WING REFLEX coordinated in medulla. vs. vagus & glossopharyngeal nerve carry info to & from the medulla.
* During swallowing beathing inhibit, nasopharynx close, perstalsis begin, larynx elevate (glottis close), upper
esophageal sphincter relax (gravity accelerate the movement).
* At rest intraesophegeal P is < than atmospheric P, Intrathoracic P can be measured by baloon catheter.
* Primary peristalsis create just behind the food and secondary peristalsis clear the esophagus.
* Lower esophageal sphincter relax (via vagus nerve neurotransmitter is VIP) at the same time Orad stomach relax
(receptive relaxation) CCK participate in it by increasing dispensability of Orad stomach.

* G a stric re flux ---- occur when tone of esophageal sphincter + or secondary peristalsis does not clear food particles.
* Ac ha la sia ---- when lower esophageal sphincter does not relax, in turn food accumulates in esophagus.
* O ra d re g ion ---- contain Oxyntic gland vasovagal reflex relax Orad region. (Oxyntic gland secrete Hc l and Intrinsic fa c tor)
* C a ud a d re g ion ---- contraction, mixing occur and food propel to doudenum.

* M IG RATING M YO ELEC TRIC C O MPLEX :-
* Are contraction that occur at 90 min interval during fasting which clear stomach. Motilin cause those contraction.
* Gastric emptying is fast when contents are isotonic and is slow when contents are hypertonic or fatty.
* H+ in doudenum inhibit gastric emptying by direct neuronal reflex via GI plexus.
* Se g me nta l c ontra c tion ÷ mixing of contents in orad and caudad direction but no net movement of food occur .
* Pe rista ltic c ontra c tion ÷ coordinated by enteric nervous system & propel food downward.( contrac tion behind bolus
and relaxation in front of bolus )
* G a stroile a l re fle x ÷ deliver intestinal content in colon. Reflex mediated by ANS and gastrin.
* Ha ustra is a sac like segment appear following segmental contraction of colon (during mixing the colon content).
* Once rectum is filled about 25% cause urge to defication (it can be prevent by voluntarily by external sphincter).
* Va lsa lva ma ne uve r :- voluntary increasing of intraabdominal P by expiring against closed glottis.
* Food in stomach ÷ | gastro colic reflex ÷ | frequency of mass movement.
* Parasympathetic activity cause rapid gastrocolic reflex whereas CCK & Gastrin slows down the gastrocolic reflex.
* G a stroc olic re fle x : Is food in stomach which | the motility of the colon and frequency of mass movement.








KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
12


--------------------------------------------------------------------------------------------------------------------------------------------------------------------------
G I SEC RETIO N C O NTENTS STIM ULATED BY I NHIBITED BY
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Saliva | HCO3 , | K+ IP3 parasympa thetic (imp) Sleep
Hypotonic c AMP sympa thetic ( | ) Dehydra tion
o a mylase (starch) Atropine (anticholinergic)
Lingual lipase (triglyc erides)
Kellikrein
Gastric HCl Gastrin, Ac h, + PH of stomac h
Hista mine (H2) via c AMP Chyme in doud enum
Atropine, Cemetidine, vagotomy, omeprazole
Pepsinogen parasympa thetic
Intrinsic fa c tor
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
C ELL TYPE SITE PRO DUC T STIM ULUS FO R SEC RETIO N
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Oxyntic (parieta l c ell) Fundus HCl Gastrin, Hista mine, Ac h (vaga l)
Intrinsic fac tor
Chief cell (p ep tic cell) Fundus (Body) Pepsinogen Ac h (vagal stimula tion)
(convert to pepsin a t low PH)
G cell Antrum Gastrin see above
Mucous c ells Antrum mucous, pepsinogen Ach (vaga l stimula tion)
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* G a stric Se c re tions --- HCl is secreted by parietal cell into lumen of stomach and HCO3 absorbed in blood stream
and HCO3 absorbed in venous blood (Alkaline Tide) later it secreted back into the lumen of the GI tract via
pancreatic secretion to neutralize H+ in small intestine.
Fig:














* Chief cells secret Pepsinogen in the form of zymogen granules.
* When stomach is empty its PH is < 3.0 ÷ inhibition of gastrin release, which further inhibit H+ secretion via
somatostatin.
* Chyme in the doudenum inhibit H+ secretion directly or via hormone GIP (release by fatty acid in stomach) &
Secretin (release
by H+ in duodenum).
* In gastric ulcer H+ is lower than normal and Gastrin is |.
* In duodenal ulcer H+ is higher than normal, Gastrin is high | and Gastric perital cells are | because of gastrin
mediated growth.
* Zollinger Ellison $ --- Gastrin secreting tumor of pancreas ÷ | H+ secretion & is not subject to - ve feedback
inhibition of H+.
* In vomiting H+ is lost and results into Metabolic Alkalosis (arterial Blood become Alkaline)
---------------------------------------------------------------------------------

KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
13


* PANC REATIC SEC RETIO N :-
* Pancreatic juice is high in vol having same Na+, K+ conc as plasma where as HCO3 conc is higher than plasma,
and Cl- conc is lower than plasma.
* Pancreatic juice has isotonicity. It contain lipase, amylase, protease.
* Aqueous component is varies with flow rate.
* Na+, K+ conc is not effected by flow rate ( vs. saliva )
* At low flow rate HCO3 is low and Cl- is high where as At high flow rate HCO3 is higher and Cl- is low.
* The Acinar cell produce initial pancreatic juice Na+ and Cl-, than Ductal cell modified it by secreting HCO3 and
absorbing Cl- ( HC O 3 - C l e xc ha nge ) . Pancreatic duct is permeable to H2O so make it isosmotic.

* Re g ula tion of Pa nc re a tic se c re tion :- It is regulated by secretin and CCK.
* Secretin acts on pancreatic ductal cell ÷ | HCO3 secretion (via c AMP) where as CCK acts on Pancreatic Acinar cell
÷ | enz secretion (via IP3).
* Ach (via vagal reflex) stimulate enz secretion by Acinar cell in response to H+, small peptide, AA, fatty acid in
duodenum.
* Cystic Fibrosis --- Defect in Cl channel because of mutation in the Cystic fibrosis Transmembrane conductance
(CFTR) gene Which results into deficiency of pancreatic enz ÷ mal absorption (statorrhea).
-----------------------------------------------------------------------------------------------------

BILE SEC RETIO N AND G ALL BLADDER:-
* Bile contain bile salts, phospholipids, cholesterol, bile pigment(bilirubin).
* Bile salt are Amphiphatic having hydrophobic and hydrophilic portion.
* In water bile salt orient them selves around droplet of lipid and keep the lipid disperse in solution (emulsified).
* Bile salt form Micelles by covrering one fatty acid and two monoglycerides; pointing there hydrophilic portion into
the aqueous solution to make it soluble for absorption.
* Bile is produce by hepatocytes continuously (chloretic agent increase bile formation).
* primary bile acid (cholic acid and chenodeoxycholic acid) is syn in hepatocytes than conjugate it to glycine and
Taurine to form the respective bilesalt.
* Intestinal bacteria convert primary bile acid to secondary bile acid (deoxycholic acid and lithodeoxycholic acid).
* Gall bladder concentrate the bile by NaCl and HCO3 reabsorption where as water reabsorbs isosmotically.
C O NTRAC TIO N O F G ALL BLADDER :-
* CCK cause contraction of gall bladder & relax sphincter of Oddi. vs.
Ach cause only contraction of Gall bladder.
* Terminal ileum absorbes conjugated bile acid with Na+ by sec active transport.
* Bile depletion cause statorrhea, bile pool depletion and Anemia, for e.g. Due to ilieal resection or diseased ileum.
----------------------------------------------------------------------------------------------------

DIG ESTIO N AND ABSO RPTIO N :-
+ C ARBO HYDRATE - - Absorbs only in the form of monosaccharide (glucose, galactose, fructose).
* o Amylase (salivary and pancrea tic) hydrolyze 1,4 glycosidic bond in starch & yield oligosaccharides maltose, maltriose,
& o limit dextrin which is further hydrolyze to yield glucose, galactose & fructose by enz maltase, o dextranase &
sucrase (brush border enz).
* Lactase, Trehalase also yield monosaccharide form disaccharides.
* Glucose and galactose absorbs with Na+ as a sec active transport, where as Na - K pump at basolateral side
maintain IC Na+. If this pump is poisoned Glucose, galactose absorption stops.
* Glucose, Galactose entered the intestinal cell by Na+ dependant Sec active transport (Cotransport) later it
entered blood by facilitated diffusion.
* Fructose absorption in the intestinal cell occur by facilitated diffusion ( so can not absorb against its | gradient).
* Lactose intolerance occur when brush border lactase is + or absent ÷ lactose cant be absorb ÷ H2O remains in
lumen ÷ results in osmotic diarrhea.




KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
14


+ PRO TEIN - - Absorbs as a AA, Dipeptide and Tripeptide in intestinal cell.
* End op e p tid a se hydrolyze interior peptide bond, vs. Exope ptid a se hydrolyse one AA at a time from C terminal .
* Pe p sin secreted as pepsinogen from Chief cells H+ converts it into pepsin.
* PH for pepsin is 1 – 3, PH more than 5 inactivate pepsin as in duodenum. Pepsin is not essential for protein digestion
* Pa nc re a tic p rote a se are secreted in inactive form which is activated by brush border enz. eg Tripsinogen is
converted to Trypsin (active form) by Enterokinase in small intestine.
* Dipeptide and Tripeptide must hydrolyse by cytoplasmic peptidase to AA prior to enter into the blood.
* Free AA, Dipeptide and Tripeptide absorb with Na+ as sec active transport than AA enters blood by facilitated
diffusion.
* Dipeptide & Tripeptide absorbs faster than free AA due to 4 separate carriers for acidic, basic, neutral & Imino AA
absorption.
* Pancreatic protease degrade each other and also absorbed along with dietary protein.
+ LPIPDS - - Absorbs as fatty acid, monoglycerides & cholesterol in the form of micelles. (Glycerol is hydrophilic & is not
contain in micelles)
* Lingual Lipase digest some lipids, stomach breaks lipid into droplets and intestinal bile emulsify it.
* Pancreatic lipase, cholesterol ester hydrolase & phospholipase A2 hydrolyze lipids into fatty acid, monoglyceride
& chlesterol.
* Intestinal cells reesterified Triglycerides, phospholipids with cholesterol and apoprotein form chylomicron & than
chylomicron transported out of cell by exocytosis in the lymphatics later chylomicron added to the blood via
thoracic duct.
* Abetalipoproteinemia is failure to synthesize Apoprotein | results in inability to transport Chylomicron out of cell.
(apoprotein is one of the constituents of chylomicron).
* Hyper secretion of gastrin ÷ | H+ secretion ÷ + PH in duodenum ÷ Inactivate pancreatic lipase ÷ Statorrhea.

ABSO RPTIO N O F ELECTRO LYTE AND WATER :- Occur by cellular and paracellular routes.
+Tig ht Junc tion are - Tight (impermeable) junction present in epithelium of colon.
- Leaky (permeable) junction present in epithelium of small intestine and gall bladder.

NaCl absorption ------- 1. Passive diffusion (Na+ channel) 2. Na+ glucose, Na+ AA co transport.
3. NaCl cotransport. 4. Na+ - H+ exchange.

* In colon Na+ channel are stimulated by Aldosterone.
* Na+ - K pump ÷ + IC Na+ conc on basolateral side.
* Cl- absorption accompanies Na+ absorption through out the GI tract by -- 1. NaCl co transport
2. Cl - HCO3 exchange
3. Cl diffuse passively by paracellular route.

* K+ absorbs by passive diffusion (via paracellular route in small intestine) where as K+ secreted actively by
aldosterone in colon In diarrhea K+ secretion is | in colon  hypokalemia.
* H2O absorbs in small intestine and gall bladder osmotically. Where as colon is less permeable to water.

SEC RETIO N O F ELEC TRO LYTE AND H2O :- Secretive mechanism is located in Crypt. vs. absorptive mechanism is in Villi.
* Cl is primary ion secreted in intestinal lumen through Cl- channel (via cAMP) and Na+ follow Cl- where as water
follow them.
* Cholera toxin some E- Coli toxin activate adenylate cyclase at the basolateral mem of the crypt ÷ | IC cAMP ÷
| Cl secretion ÷ Na+ and H2O follow Cl- ÷ Diarrhea.
VITAMINS :- Fat soluble vit absorbs along with lipid and water soluble vit absorbs with Na+ cotransport where as VitB12
together with Intrinsic factor absorbed in ileum.

* C a ++ :- Ca++ absorption depend on active vit D (1,25 dihydroxycholecalciferol). ( + vit D cause Rickets and Osteoma lacia )
* Iron :- Iron absorbes as heme iron ( bound to hemoglobin or myoglobin ) or as a free Ferrous (Fe++). In Intestine cells
Heme iron broke down to release iron which bind to Apoferritin and transport to blood than In blood it
bound with Transferrin which take iron to liver and store it. (Iron deficienc y is the most common cause of anemia)
------------------------------------------------------------------------------------
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
15

RENAL AND AC ID BASE PHYSIO LO G Y
* TBW -- 60% of body wt. ( TBW vol is measured by Titra ted H2O or D2O)
* ICF -- 2/ 3 of TBW and is measured by TBW - ECF. ( it contain K+, Mg++, Protein, Inorganic ph, ATP etc)
* ECF --1/ 3 of TBW a nd is measured b y sulfa te, inulin, or manitol. (it contain Na+, Cl-, HCO3).
* Plasma -- ¼ of ECF or 1/ 12 of TBW & is measured b y radioiodinated serum albumin RISA or evan blue.(it contain Albumin a nd Globulin etc )
* Interstitial fluid --- ¾ of ECF ( ¼ of TBW ) and is measured b y ECF - Plasma.
* Fluid Compartment -- is measured b y vol = a mount injec ted - a mount exc reted / conc in plasma.
-------------------------------------------------------------------

* RBF (renal blood flow) is 25% of cardiac out put.
* RBF remain constant over the range of arterial BP from 100 - 200 mmHg (auto regulation).
* RPF (renal plasma flow) measured by PAH clearance because PAH is both filtered and secreted by renal tubules.
* Rena clearance can be measured by C = UV/ P RPF = c PAH = [U] PAH V / [P] PAH

* GFR is 20% of renal plasma flow (RPF) 125ml/ min. G FR = [U] inulin V / [P] inulin.
* GFR is measured by Inulin clearance because Inulin is filtered but not reabsorbed or secreted by renal tubules.
* Both BUN and Plasma Creatinine | as GFR +.
* Filtration Fraction is the fraction of RPF that filter across the glomerular capillaries ( it is 0.20). thus 20% of RPF is filtered.
Filtra tion Fra c tion = G FR / RPF
* GFR can be expressed by Starling equation. G FR = Kf [ ( PG c - PBc ) - ( tG c - tBc ) ]

* PG c : -- is constant along the length of capillaries.
It | by dilatation of afferent arterioles &| by constriction of efferent arterioles.
* PBc : -- | by constriction or blockade of ureter ÷ + GFR.
* tG c :-- | along the length of glomerular capillaries. It | by | in protein conc ÷ + GFR.
* tBc : -- is zero small amount usually absorbs

* NaCl and Mannitol donot cross cell mem and confined to ECF,
* More water than salt lost during sweating.

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
TYPE EXAM PLE EC F Vol IC F Vol EC F O smola rity Hc t, Se rum Na +
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
- Isosmotic Vol Expansion Isotonic Na cl infusion | No change No Change + Hc t , Na --
- Isosmotic Vol Contra c tion Diarrhea + No change No change | Hc t , Na --
- Hyp erosmotic Vol Contrac tion Swea t, fever, Diabetes Insipidus + + | Hc t (RBC shrunk) Na+ |.
- Hyp erosmotic Vol Expansion | NaCl intake | + | Hc t + ,Na+ | .
- Hyposmotic Vol Expansion SIADH | | + Hc t (RBC swell), Na+ +
- Hyposmotic Vol Contra c tion Adrenocortica l insufficiency (loss of NaCl) + | + | Hc t, (RBC swell) Na+ +.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* TRANSPO RT M AX CURVE FO R G LUC O SE :- Plasma glucose conc of < 300 mg/ dl can be absorbed by proximal tubule
through Na - glucose co transport.
* Threshold at which glucose first appear in the urine is approx 300 mg/ dl.
* SPLAY is the region of glucose curve b/ w Threshold and transport max. (300-350mg/ dl)
* At 300 - 350 mg/ dl --- spilling of gluc ose occ ur in urine b e fore sa tura tion or ( Tm) Transport maximum.

* Tm C URVE FO R PAH :- PAH filtration | as PAH plasma conc |.
* Secretion of PAH from Peritubular capillaries into tubular fluid occur in proximal tubule.
* PAH secretion | when plasma conc | once carriers become saturated it stops further | in secretion due to Tm.
* RPF is measured at plasma PAH conc below the Tm (Transport max).
* Relative Clearance: PAH > K+ > inulin > urea > Na+ > glucose > AA > HCO3-.

* Na + REG ULATIO N: Na+ in the tubular fluid (TF) in Bowman space equals that in plasma (P) is said to be TF/ PNa+ = 1.0
* If TF/ PNa+ is < 1 Net Reabsorption of solute occur  dilution of TF.
* If TF/ PNa+ is > 1 secretion of solute occur  produce concentrated TF.
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
16


* Only 1% of filtered Na+ is excreated.
* Na+ is reabsorbed by Co transport with glucose, AA, ph, lactate, K+ in proximal tubule.
* Na+ is reabsorbed also by Counter transport as Na+ - H+ exchange in PT.
* Na+ absorbed with Cl- in middle and late PT. (total of 67% of Na+ reabsorbed in PT)
* In Thick ascending limb of Loop of Henle 20% of Na+ reabsorbed as Na+ - K+ - 2Cl- Cotransport
also called diluting segment and is impermeable to H2O (loop diuretics act here).
* Distal tubule and Collecting duct together reabsorbe 12% of filtered Na+.
* Early Distal tubule is Cortical Diluting segment reabsorb Na+ by Na+ - Cl- Co transport. (Thiazide ac t here).
* Principle cell reabsorb Na+ & secrete K+ in late distal tubule (DT) & collecting duct. (Aldosterone/ ADH ac t here)
* Intercalated cell secrete H+ & reabsorb K+ in late DT& collecting duct. (Aldosterone also ac t here to secrete H+).
* Starling forc es in p eritubular capillaries (due to | or + in protein conc)  | or + in proximal tubular reabsorp tion.

* K+ REG ULATIO N :- K+ is filtered, secrete & reabsorbed by nephron to achieve K+ balance.
* TF/ PK+ = 1 in Bowman space.
* PTreabsorb 67% of K+ alonge with Na+ and H2O.
* Thick ascending limb of Loop of Henle reabsorb 20% of filtered K+ as Na+ - K+ - 2Cl- Cotransport.
* Distal Tubule and collecting duct either reabsorb or secrete K+ depend on dietary intake.

SHIFT O F K+ b / w EC F AND IC F
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
C a use s of K+ shift out of c e ll ( hyp e rka le mia ) C a use s o f K+ shift into the c e ll ( hyp oka le mia )
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
* Insulin Deficienc y * Insulin
* | adrenergic antagonist * | agonist
* Acidosis ( via H+ - K+ exchange ) * Alkalosis ( via H+ - K+ exchange)
* Hyperosmolarity (H2O out of c ell K+ follow) * Hyposmolarity (H2O flow into the c ell K+ follow)
* Na+ - K+ pump inhibitor
* Excersize
* Cell lyses
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
EFFECT O F DISTAL K+ SEC RETIO N
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
C a use s of | d ista l K+ se c re tion C a use s of + d ista l K+ se c re tion
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
* High K+ diet * Low K+ diet
* Hyp eraldosteronism * Hypoaldosteronism
* Alkalosis * Acidosis
* Thiazide * K+ sparing Diuretics
* Loop diuretics * Renal failure
* Luminal Anion
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* Ure a Re g ula tion : 50% of urea reabsorb passively in PT. Other segment are impermeable to urea.
* ADH | urea permeability of inner medullary collecting duct which contribute urea recycling in the medulla.

* Phosp ha te Re g ula tion : 85% of phosphate reabsorb in PTas Na+ - phosphate Cotransport. Where as 15% excreted.
* PTH Inhibit phosphate reabsorption ÷ phosphaturia & | urinary cAMP. ( PTH also | bone resorp tion )
* phosphate is urinary buffer for H+ ÷ excretion of H2PO4 (titrableacid).

* C a ++ Re g ula tion : 90% of Ca++ reabsorbed in PTand Thick ascending limb of Loop of Henle.
* Loop diuretics cause | Ca++ excretion by inhibiting Na+ reabsorption. ( Tx of hypercalcemia )
* Thiazide + Ca++ excretion by reabsorbing Ca++ in distal tubule ( Tx of Hypercalciurea ).
* DTand Collecting duct reabsorb 9% of Ca++ actively.
* PTH | Ca++ reabsorption in DT.
* Mg ++ Re g ula tion : Reabsorb in PT, Thick ascending limb and DT
* In Thick ascending limb Mg++ and Ca++ compete for reabsorption.
* Mild + in Mg++ ÷ stimulate PTH secretion ÷ | Ca++ reabsorption.
* Severe + in Mg++ ÷ inhibit PTH secretion ÷ | Mg++ reabsorption.( also | Phosphate reabsorption )
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
17


* C O NC AND DILUTIO N O F URINE :-
* Cortic op a p illa ry osmotic g ra d ie nt :
* Is the gradient of osmolarity from cortex ( 300 mOsm / L) to papilla (1200 mOsm / L) & is comprise primarily of NaCl & urea.
* Vasa Recta (capillaries of Loop of henle) maintain the corticopapillary gradient by serving as osmotic exchanger.
* Thick Ascending loop of henle reabsorbe Na+ - K+ - 2Cl by cotransport & is permeable to H2O. [ TF/ Plasma osmo = <1 ]
* Early distal tubule is cortical diluting segment and is impermeable to H2O.
* In late distal tubule H2O permeability | by ADH. Here H2O reabsorb normally until TF/ Plasma Osmo = 1
* In collecting duct H2O permeability | by ADH. Here H2O reabsorb normally untill TF/ Plasma Osmo >1 .

HO RM O NES THAT ACTS ON KIDNEY:
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Hormne s Stimulus for se c re tion Time c ourse M e c h o f a c tion Ac tion on kid ne y
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
PTH + Plasma Ca++ Fast Ad enyla te Cyc lase + ph reabsorp tion (PT)
mild + in Mg++ c AMP (a t basola teral side) | Ca++ reabsorption (DT)
Stimula te 1 o hydroxylase in PT
ADH | Plasma Osmolarity Fast Ad enyla te c yclase | H2O p ermeability in la te DT&
+ Blood vol V2 Rec ep tors collec ting duc t (principle c ell)
Aldosterone + Blood vol (via renin AT) Slow New Protein Synthesis | Na Reabsorp tion in DT- Principle c ell
| Plasma K+ | K secretion in DT- Principle cell
| H+ secretion in DT- Interca lated c ell
ANF | Atrial Pressure Fast Guanyla te c yclase | GFR, + Na+ reabsorption
cGMP
Angiotensin + Blood vol (via renin) Fast IP3 mec h | Na+ - H+ exchange in PT
(stimula te Aldosterone synthatase)
| HCO3 reabsorption in PT
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

AC ID BASE BALANC E :
* Buffer prevent changes in the pH when H+ ions are added or removed. ( Buffer is most effective in the linear
portion of the titration curve.)
* Buffer are more effective with in 1.0 pH unit of the pK.
* Major EC buffer is HCO3. (pK of CO2/ HCO3 buffer is 6.1)
* Minor EC buffer is Phosphate (PK of H2PO4 / HPO4 2 buffer is 6.8)
* Major IC buffer is Hg. Deoxyhemoglobin is Better buffer than Oxyhemoglobin at physiologic pH.
* Minor IC buffer is organic Phosphate (AMP, ADP, ATP, 2,3 DPG)
* When pH of the solution is equal to pK than there are equal conc of HA- and A-.
* PH = pK + log [A-]/ [HA-] . (where A- is base of the buffer and HA- is acid of the buffer)

RENAL ACID BASE :
* Filtered HCO3 reabsorbs in proximal tubule in two steps
* | PCO2 ÷ | HCO3 Reabsorption ( because IC H+ is | )
* + PCO2 ÷ + HCO3 Reabsorption ( because IC H+ is + )
* ECF vol contraction ÷ | HCO3 Absorption (contraction Alkalosis) and produce acidic urine.
* ECF vol expansion ÷ + HCO3 Reabsorption .
* Angiotensin II stimulate Na+ H+ exchange ÷ | HCO3 reabsorption. (Contributing to Contraction Alkalosis)
-----------------------------------------------------------------------------------------------

* H+ secrete in the lumen by H+ - ATPase and resultant HCO3 is reabsorbed.
* Secreted H combine with filtered HPO4 ÷ H2PO4 (titrable acid). This Process results into net excretion of H+ in
urine.
* Another mech for excreting H+ is NH3 Production in renal cell from glutamine. ( NH3 produc tion | in Acidosis which favor H+
excretion ) H+ + NH3 ÷ NH4+ excreted in urine (diffusion trapping)




KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
18


AC ID BASE DISO RDER:
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
DISO RDER C O 2 + H2O ÷÷ H + HC O 3 Re sp C omp e nsa tion Re na l C o mp e nsa tion
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Metabolic Acidosis + | + Hyp erventila tion | H+ excretion
| HCO3 rea bsorption
Metabolic Alka losis | + | Hypoventila tion | HCO3excretion
Respiratory Acidosis | | | None | H+ excret ion
| HCO3 rea bsorption
Respiratory Alka losis + + + None + H+ Excretion
+ HCO3 rea bsorption
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* RULE : CO2 goes up HCO3 goes up CO2 goes down HCO3 goes down. ( Direc tly proportional rela tionship).
* Normal Serum Anion Gap is 10 - 16 mEq / L. ( Serum Anion Gap = [Na+] - [Cl-] - [HCO3-] )
* Synthesis of Glucose (gluconeogenesis) during prolong fasting also occur in kidney.
* H+ Excreted in urine as H+ + HPO4 -2 ÷ H2PO4 (Titrab le acid)
H+ + NH3 ÷ NH4+ (diffusion trapping)

-------------------------------------------------------------------------------------------------------------------------

RESPIRATO RY PHYSIO LO G Y
* LUNG VO LUM ES :
1. Tid a l Vol - - is the vol inspired and expired with each normal breath.
2. Insp ira tory Re se rve Vol ( IRV) - - is the vol that can be inspired over the tidal vol eg during exersize.
3. Exp ira tory Re se rve Vol ( ERV) - - is the vol that can be expired after expiration of the tidal vol.
4. Re sid ua l Vol ( RV) - - Vol that remains in the lung after max expiration. ( cant be measure b y spirometery ).

* Ana tomic De a d sp a c e -- Vol of conducting airway it is 150 ml normally. (measured by Fowler’ s Method )
* Physiolog ic De a d sp a c e -- vol of the lung does not eliminate CO2 normally or due to dis. ( measured by Bohr’ s Method )

* M inute Ve ntila tion = Tid a l Vol × Bre a th / min
* Alve ola r ve ntila tion = Tid a l Vol ÷ De a d sp a c e × Bre a th / min

* LUNG C APAC ITIES :
1. Insp ira tory C a p a c ity = Tid a l Vol + Insp ira tory Re se rve Vol.
2. Func tiona l Re sid ua l C a p a c ity ( FRC ) = Exp ira tory Re se rve Vol + Re sid ua l Vol (can not measured by spirometery)
3. Vita l C a p a c ity = Tid a l Vol + Insp ira tory Re se rve Vol + e xp ira tory Re se rve Vol
4. Tota l Lung C a p a c ity = Tid a l Vol + IRV + ERV + RV.

* Forc e d Exp ira tory Vol ( FEV) : Is air expired in one Second after Max Inspiration.
It is 80% of forced vital Capacity. FVC . FEV / FVC = 0.8
* In restrictive Lung Dis ( Fibrosis ) both FEV and FVC is reduced.
* In Obstructive Lung Dis ( asthma ) FEV reduces more than FVC.

* MUSC LE O F INSPIRATIO N : * MUSC LE O F EXPIRATIO N :
Diaphragm (normally) Passive (normally)
External Intercostal Muscle Abdominal & Internal Intercostal muscle ( during exercise )
Accessory Muscle ( during exercise )

* C OM PLIANCE :- The extent to which lung expand (stretchability) for each unit in Transpulmonary P is called the
Compliance.
| Compliance ÷ | Stretchability where as + compliance ÷ + stretchability. ( Comp lianc e measures stiffness of the lung )
( C ha ng e in Intra p le ura l P d uring insp ira tion is use d to me a sure d yna mic c o mp lia nc e of the lung )




KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
19

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
* C a use s of + Lung Comp lia nc e * C a use s of | Lung C omp lia nc e
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
High Expanding Pressure Emphysema (+ Elastic fiber)
| Pulmonary venous return Age
Fibrosis
Lack of surfa c tant
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* Under equilibrium condition lung have a tendency to collapse which is exactly balance by tendency of chest wall
to spring out.
* HYSTERESIS :- Is inflation of the lung follow different curve than deflation of the lung.
* Compliance of the lung chest wall system is less than the lung alone or chest wall alone.
* In Emphysema lung compliance is | so FRC | too. This change disturb the lung chest compliance system, so the
lung chest wall system seek for higher FRC in order to balance these two forces again. This is the reason pt develop
barrel shape chest to provide new Vol to lung with results into + O2 diffusion.

* SURFACE TENSIO N O F ALVEO LI AND SURFAC TANT :
* Tendency to collapse alveoli is directly proportional to the surface tension and inversely proportional to alveolar
radius called La p la c e La w . ( large a lveoli has low tend ency to collapse than sma ller a lveoli ).
* Surfactant lines the alveoli and reduce the tension ÷ | compliance.
* Surfactant is made by Type II alveolar cells consist of Dipalmitoyl Phosphatidyl Choline.
* Neonatal RDScause by lack of surfactant ÷ Atelactasis (difficulty in reinflation due to + compliance) ÷ Hypoxemia
(V/ Q misma tch).

* AIRWAY RESISTANC E :- Airflow is directly proportional to pressure difference of the mouth and alveoli and inversely
proportional to airway resistance . (Airflow) Q = AP/ R ( where AP is pressure gradiant and R is Airway Resistanc e)
* Airway Resistance (R) is describe by Poise uille ’s La w . R = 8nl / t r4
Where n is viscosity of the inspired air, l is length of airway, and r is radius of airway.

* Fa c tor tha t c ha ng e Airwa y Re sista nc e :
* Parasym stimulation, Irritants, Slow reacting subs of anaphylaxis (constricts airway) ÷ + radius and | resistance
* Sympathetic stimulation dilates airways ÷ | Radius and + Resistance (via |2 recep tors).

* | Lung Vol exert more traction (pulling force) & + airway resistance. vs.
+ Lung Vol exert less traction & | airway resistance
For exa mple in Asthma p t learn to brea th a t high lung vol to off set the high resistanc e.

* Viscosity & Density changes the resistance to air flow : If density of gas | ÷ resistance to airflow | (eg deep sea diving)
If density of gas + ÷ resistance to airflow + (brea thing low density gas like helium)
* Medium size bronchi are major site of resistance.
* Small size airway do not offer | resistance because of parallel arrangement.
-----------------------------------------------------------------------------------------------

BREATHING C YC LE :- ( At rest before inspiration begin)
1. At Re st - - - Alveolar P equals atmospheric P ( alveolar P is said to be zero ).
Intrapleural P is - ve ( can be measured b y baloon ca theter in esophagus ) where as Lung vol is FRC.
2. During Insp ira tion - - Inspiratory muscles contract ÷ thorax Vol to |.
P gradient cause air to flow into the lung.
Intrapleural P become more - ve and lung Vol | by 1 tidal vol (+ FRC).
3. During Exp ira tion - - - Alveolar P become greater (+ ve) than atmospheric P.
Intrapleural P return to its resting value during normal expiration (passively).
During forced expiration Intrapleural P become +ve Lung vol return to FRC before another cycles begin.
( In COPD airway resistanc e is | & p t expires slowly with pursed lip to prevent airway collapse which occur with forc ed expira tion )
* G a s Exc ha ng e :- * Diffusion of gases such as O2 and CO2 depends in the partial P difference across the mem and
area available for diffusion. ( Can be measured by Da lton’ s Law Partial P = Total P × Frac tional conc entra tion ).
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
20


* About 2% of Cardiac output bypass pulmonary circulation because of physiologic shunt that’ s why
mixture of the venous blood makes PO2 of arterial blood slightly less than alveolar air.
* Solubility of O2 in the blood is 0.3 ml/ 100ml of blood .

Blood g a se s va lue in norma l c ond itions:
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
G a s Dry Insp ira tion Humid Insp ira tion Alve ola r Air Sys Arte ria l Blood M ixe d V e nous Blo od
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
PO2 160 mmHg 150 mmHg (due to H2O in air) 100 100 % (slightly less) 40 mmHg
PCO2 0 40 mmHg 40 mmHg 46 mmHg
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

* Pe rfusion limite d e xc ha nge --- When gas equilibrate early along the length of pulmonary capillaries the partial P of
arterial blood become equal to partial P of alveolar air.
* Diffusion limite d e xc ha ng e - - - When the gas does not equilibrate fully by the time blood reaches the end of the
pulmonary Capillaries the partial P of arterial blood is less than that of alveolar air .
* Diffusion of O2 from alveolar air to pulmonary capillaries bed is usually perfusion limited but become diffusion limited
in dis. Eg In Fibrosis diffusion of O2 + because of thickening of the alveolar mem ÷ | diffusion distance. Where as in
Emphysema diffusion of O2 + because surface area for diffusion is +.
------------------------------------------------------------------------------------------------
O 2 TRANSPO RT :
* Hg contain 4 subunit 2o and 2| ( each subunit contain heme moiety which is iron containing porphyrin ) .
* Ferrous (Fe2+) state of iron bind O2 Where as ferric (Fe3+) state of iron is methemoglobin and does not bind O2.
* In fetal Hg | chain is replaced by ¸ chain.
* O2 affinity of fetal Hg is higher than adult because 2,3 diphosphoglycerate (DPG) bonds less avidly to fetal Hg. ( that
is why O2 movement from mother to fetus is facilitated ).
Hg O 2 DISSOC IATIO N C URVE :
* At PO2 of 100 mmHg ÷ Hg is almost 100% saturated.
* At PO2 of 40 mmHg ÷ 75% of Hg is saturated.
* At PO2 of 25 mmHg ÷ 50% of Hg is saturated.
* The affinity of 4
t h
O2 molecule is very high.

* Because the curve is almost flat in PO2 range from 60 - 100 mmHg, the human can tolerate change in atmospheric
P without compromising the O2 carrying capacity of Hg.

C HANG E IN O 2 DISSO CIATIO N C URVE :
1. Shift to the rig ht - - - Affinity of Hg for O2 + ÷ P50 | . ( C a use s a re |PC O 2, +PH, |Te mp, | 2,3DPG) .
* Adaptation of chronic Hypoxemia (high altitude) ÷ | 2,3DPG which bind to | Chain to facilitate unloading of O2 in
tissue. By + the affinity of O2 .
* | PCO2 and + PH + the affinity of Hg for O2 & facilitating the unloading of O2 in tissue as in exercise. ( Bohr’s Effe c t )
2. Shift to the Le ft - - - Affinity of Hg to the O2 | ÷ P50 + ÷ unloading of O2 in tissue is more difficult .
* C a use s a re + PC O 2, | PH, + Te mp , + 2,3DPG .

C O 2 TRANSPO RT : CO2 carried to the lung in 3 Forms. 1. HCO3- ( 90% .major form )
2. Carbaminohemoglobin ( small amount )
3. Dissolved CO2 ( small amount )
* CO2 generate in tissue ÷ enter into venous plasma ÷ enter into RBC where CO2 combine with H2O by Carbonic
anhydrase ÷ H2CO3 ÷ H+ and HCO3-.
* H+ is buffered inside RBC (Deoxyhemoglobin) where as HCO3- is exchanged for Cl- by RBC (C loride shift).
* In lung all above reaction occur in reverse ( which is HCO3- enter into RBC in exchange for Cl- than HCO3-
combines with H+ ÷ H2CO3 which further decompose into CO2 and H2O and CO2 is diffuse out ).

* Pre ssure and Re sista nc e in pulmonary circulation is much lower than systemic circulation.
* Cardiac output (pulmonary) is equal to systemic circulation.

KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
21


DISTRIBUTIO N O F PULM O NARY BLO O D FLO W --- Distribution of pulmonary blood flow effect by gravity.
* In supine position blood flow is uniform through out the lung where as standing position blood flow is lowest in apex.
BLO O D FLO W IN LUNG ZO NES :
+ Zone 1 - - Alveolar P > Arterial P > Venous P (b lood flow is lowest) -- V/ Q |. (| Alveolar P collapses the capillaries when arterial BP is low eg .In
Hemorrhage)
+ Zone 2 - - Arterial P > Alveolar P > Venous P (b lood flow is medium).
+ Zone 3 - - Arterial P > venous P > Alveolar P (b lood flow is highest) -- V / Q + .
* Hypoxia cause local vasoconstriction (Opposite effect of that in systemic circulation where hypoxia cause
vasodilation) . It is imp in lung because local vasoconstriction divert blood from poorly ventilated area to well
ventilated area.
* In fetus pulmonary vascular resistance is very high due to generalized hypoxic vasoconstriction as a result blood flow
through fetal lung is low . ( with first breath alveoli become oxygenated and vascular resistance decreases )
* Both ventilation and Perfusion is great in base than in apex. ? (very imp to understand)
* Right to left shunt normally occur to a small extent because 2% cardiac output by passes the lungs. More than 2% is
Usually due to congenital abnormality  + in arterial PO2. Where as Left to right shunt  | in venous PO2 (donot result
in a + in arterial PO2)

VENTILATIO N / PERFUSION RATIO :
1. Norma l V/ Q Ra tio = 0.8 ( 0.8 when tidal Vol & pulmona ry cardiac out put are normal, and it is liable for 100 mmHg of PO2 & 40 mmHg of
PCO2).
2. V/ Q is Ze ro when airway is completely blocked, Perfusion is normal and ventilation is Zero ÷ No Gas Exchange.
3. V/ Q is Infinity when blood flow is blocked and ventilation is normal ÷ No Gas Exchange.

* V/ Q is highest ( > 1.0 ) in the apex of the lung and lowest ( 0.8 ) at the base of the lung. (imp to understand)
* PO2 is greater than PCO2 in different region of lung. 1. At apex ---- PO2 | and PCO2 +
2. At base ---- PO2 + and PCO2 |
----------------------------------------------------------------------------------------
C O NTRO L O F BREATHING :-
1. M e d ulla ry Re sp Ce nte r:+Dorsa l Re sp ira tory G roup control inspiration & genera te basic rhythm of brea thing rec eive input from lung via
vagus & from peripheral chemorec ep tor via glossopharyngeal nerve where as it send output to diaphragm via
pherenic nerve .
+ Ve ntra l Re sp ira tory G roup control Expira tion & is not ac tive during norma l brea thing because Expiration is passive
.
2. Ap ne ustic c e nte r - - - - - - - - - - - - - located in the lower pons . It stimula te inspiration more d eep er and prolongs Inspira tory gasp. (Apneusis)
3. Pne umota xic Ce nte r - - - - - - - - - located in the upper pons. It inhibit inspiration therefore regula te inspira tory Vol and ra te.
4. C orte x - - - - - - - - - - - - - - - - - - - - - - - - - Breathing can be und er voluntary control.
----------------------------------------------------------------------------------------

C HEM O REC EPTO RS FO R O 2, CO 2, & H+ :-
1. C e ntra l C he more c e ptors of the me d ulla is sensitive to PH of CSF.
* H+ does not cross the BBB but CO2 does. So when CO2 enter CSF combine with H2O ÷ H2CO3 ÷ H+ + HCO3-
(by carbonic anhydrase) than liberated H+ can act directly on central chemoreceptors. ( that’ s why | or + in CO2
cause change in breathing).

2. Pe rip he ra l c he more c e ptors present in Carotid and Aortic bodies. (stimulate by + PO2, |PCO2, H+)
* When Partial PO2 falls < 60 mmHg ÷ | breathing rate by peripheral chemoreceptors.
* When PCO2 | ÷ | in breathing rate.
* H+ ion stimulate carotid bodies chemoreceptors directly and is independent of PCO2 . eg Metabolic Acidosis |
the breathing rate ( where PCO2 is low).

O THER RECEPTO RS THAT C O NTRO L BREATHING RATE :
1. Lung Stre tc h Re c e ptors ( He ring Bre ue r Re fle x ) stimula te b y distention of lung ÷ | in brea thing ra te.
2. Irrita nt Re c e ptors located in b/ w airway epithelial c ells. It stimula te b y noxious stimuli eg a mmonia, smoke etc.
3. J Re c e ptors located in a lveolar wall c lose to capillaries it stimula ted b y capillaries engorgement as in LHF  Rapid shallow breathing.
4. Joint a nd M usc le Re c e ptor ÷ | Brea thing during (early) exercise.

KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
22


INTEG RATED RESPO NSE O F RESPIRATO RY SYSTEM DURING EXERCISE :
* | O2 consumption and |CO2 production
* | ventilation rate
* No change in arterial PO2 and PCO2 where as Venous PCO2 |.
* PH stays normal during moderate exercise where as PH + during strenuous exercise due to lactic acid production.
* Pulmonary blood flow |. V/ Q rate more evenly distributed through out lung

ADO PTATIO N TO HIG H ALTITUDE :
* Alveolar PO2 + and Arterial PO2 also +.
* Ventilation rate |.
* Arterial PH | ( | Respiration cause Alkalosis )
* Hg conc | ( because | erythropoietin production )
* 2,3 DPG conc | ( facilitate unloading of O2 in tissue ).
* Hg O2 dissociation curve shift to the right side (Bohr’ s effect), + affinity of Hg for O2 and facilitate unloading O2.
* Pulmonary vascular resistance | (vasoconstriction).
-----------------------------------------------------------------------------------------------------------------

C ARDIO VASC ULAR PHYSIO LO G Y
* Stre ss Vol is the blood in systemic arteries which are thick walled.
* Arterioles are the site of high resistance and is innervated by autonomic fibers.
* Capillaries comprise of largest total cross sectional area and surface area.
* Unstre ss Vol is the blood in systemic veins and have lowest P.
* Ve loc ity of b lood flow is directly proportional to blood flow & inversely proportional to cross sectional area. v = Q / A
* Blood flows from high P to low P & is inversely proportional to resistance of the blood vessel. Q = AP/ R (Q= Flow, A= area)
* Re sista nc e is directly proportional to the blood viscosity & length of the vessel and inversely proportional to the 4
t h

Power of the vessel radius ( Poise uille ’s La w ) . R = 8ql / tr4 ( q is viscosity and l is length of vessel )
* Re nold s No: Renolds No predict whether flow is laminar or turbulent. As renold No | the tendency of turbulence|.
+ Blood viscosity ( due to anemia, + Hematocrit) | the Renold No ÷ Turbulence. ( produce audible bruits )
| Blood viscosity (eg. in narrowing of vessel, polycythemia) | the renold No ÷ turbulence. (produce bruits )

* C a p a c ita nc e ( c omp lia nc e ) describes the distensibility of the blood vessels & is directly proportional to Vol &
inversely proportional to P. C = V/ P ( V is volume where as v is flow )
* Compliance is much greater in arteries. Compliance + as person ages. ( C omp lia nc e + ÷ Pulse P | )
* Blood flow P falls over its course due to changing resistance of vessels (that ’ s why P is highest in aorta than in vena cava).
* Largest fall of P occur across the arterioles since arterioles are the site of the highest resistance.
* Arte ria l Pre ssure is pulsatile and not constant during cardiac cycle.
1. Systolic P : is highest arterial P during cardiac cycle (heart contracts)
2. Dia stolic P : is the lowest arterial P during cardiac cycle (heart relaxes)
3. Pulse P : is difference b/ w systolic and diastolic P and is determined by stroke Vol ( stroke Vol | ÷ Pulse P | )
+ in capacitance (compliance) such as with aging results in | Pulse P.( C omp lia nc e + ÷ Pulse P | )
4. M e a n Arte ria l P: is average Arterial P with respect to time calculated by Dia stolic P + 1/ 3 of Pulse P.

ELEC TROC ARDIO G RAM :
P wa ve - - Atrial depolarization ( shows the size and thic kness of a trium)
PR inte rva l - - Interval b/ w atrial depolarization & ventricular depolarization. It is starts from beginning of P wave till the
beginning of Q wave. (PR interval | when conduction velocity is slow due to heart block). NL time 0.21
Q RS c omp le x - - is Ventricular Depolarization it also buried Atrial Repolarization. Normal time 0.12
Q T inte rva l - - is beginning of Q wave till the end of Twave. It represent entire depolarization & Repolarization of
ventricle. Normal time 0.41 ( shows the size and thickness of ventric le)
ST se g me nt - - Is segment from the end of Swave till the beginning of Twave. It is isoelectric period shows entire
ventricular depolarization.
T wa ve - - is ventricle Repolarization.


KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
23


C a rd ia c AP: Na - K ATPase maintain ion gradient across cell mem. (AP are of longer dura tion in ventric le 300 m sec)
Pha se 0 : Up stroke, | inward Na flow ÷ depolarization (at the peak of AP the mem potential is equilibrium potential for Na+).
Pha se 1 : Initial repolarization caused by + inward Na+ flow and initial K+ outward flow ( it is brief period ).
Pha se 2 : Transit | in inward Ca++ flow & | outward K+ flow result in Pla te a u (outward & inward c urrent are approx same during
this p eriod)

Pha se 3 : Is repolarization in which inward Ca++ conductance + and outward K+ conductance |. | outward K+
conductance hyperpolarize the mem (equal to K+ equilibrium potential) and than resting mem potential.
Pha se 4 : Resting mem potential ( inward outward current is equal ). Resting mem potential is determined by conductance
to K+ and approaches K+ equilibrium potential.
Sinoa tria l Node ( SA) :
* It is Pace maker and does not have resting mem potential ( it exhibit Phase 4 Depolarization )
* AV Node and HISPurkinji system are latent pace maker. It can over ride SA node if SA node is not functioning.
* The intrinsic rate of Phase 4 depolarization (heart rate) is slower in AV node and HIS purkinji system than in SA node.
Pha se 4 : Slow depolarization -- | inward Na+ conductance called I ###. ( I### turn on by Repolariza tion )
Pha se 0 : Up stroke of action potential cause by | inward Ca++ flow ( it d erive mem potential toward Ca++ equilibrium potential )
Pha se 3 : Repolarization (caused by | outward K+ conduc tance)

* Phase 4 account for the pace maker activity of the SA node automaticity
( Note -- Phase 1 & 2 are not present in SA nod e ac tion potent ial )

C ond uc tion ve loc ity is the time required for exitation to spread in the heart it is fastest in purkinji system and slowest in
AV node (this is the reason EKG shows PR interval). Conduction velocity depend upon size of inward current during
up stroke.

EXITABILITY is ability of heart to initiate action potential response to inward current, during the course of action
potential changes are describe as Re fra c tory Pe riod .
1. Ab solute Re fra c tory pe riod : Begins with Action potential & end after Pleateau. AP cannot be elicited during this
period.
2. Effe c tive Re fra c tory p e riod : Slightly longer than ARP, conducted action potential can not be elicited.
3. Re la tive Re fra c tory p e riod : Period followed by ARP when repolarization is almost complete. AP can be elicited but
more than usual current is required.
-----------------------------------------------------------------------------------------------

AUTO NOM IC EFFECT O N HR & C O NDUC TIO N VELOC ITY :
* C hronotrop ic Effe c t : is | or + of HR by | or + firing of the SA nod e .
* Dromotrop ic Effe c t : is | or + of conduction velocity by slowing or speeding the conduction through AV node .
* The Atria, SA node, and AV node have parasympathetic innervation but ventricle do not.
* - ve c hronotrop ic e ffe c t + the HR by + the ra te of Pha se 4 d e p ola riza tion, the mech is + in I ### (+in Na+ c onduc tance).
* - ve d romotrop ic e ffe c t + the conduction velocity through AV node ÷ | PR inte rva l.
* Sympathetic innervation is through out the heart.
* + ve c hronotrop ic e ffe c t | the HR by | ra te of Pha se 4 d e p ola riza tion, the mech is | in I ### ( | in Na+ conduc tance ).
* + ve d romotrop ic e ffe c t | the conduction velocity through AV node ÷ + in PR inte rva l. (Ventricle filling ma y b e
compromised).
-----------------------------------------------------------------------------------------------

M YO C ARDIAL C ELL STRUC TURE :
* Sarcomeres is the contractile unit of myocardial cell it runs Z to Z. contain thick filament (myosin) & thin filament
(actin, troponin, tropomyosin)
* Intercalated disc present at Z and maintain cell to cell cohesion.
* Gap Junction present at intercalated disc, and are low resistance pathway b/ w cells. (ac count for elec trica l sync ytium)
* Ttubules continuous with cell mem ( it carries ac tion potential ) well develop in ventricle and poorly develop In atria.
* The magnitude of tension develop in heart is proportional to the | in IC Ca++. ( | IC Ca++  Ca++ triggered Ca++
release from SR )
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
24


* Ca++ binds Troponin C to remove inhibition of actin - myosin interaction by troponin - tropomyosin to cause
contraction.
* Relaxation occur when Ca++ is reaccumulated in SR by active Ca++ ATPase pump.
-----------------------------------------------------------------------------------------------

C O NTRAC TILITY ( Inotrop ism ) : Is ability of cardiac muscle to develop force at given muscle length.
* It Can be measured by Ejection Fraction ( stroke vol / end diastolic vol ) which is normally 0.55 (55%).
* Fa c tor tha t + C ontra c tility are Parasympathetic by + C a ++ e ntry into the c e ll ( - ve inotrop ic e ffe c t )

* Fa c tor tha t | C ontra c tility ( + ve inotrop ic e ffe c t ) :
1. | HR (In +ve Stair case or Bowditc h Stair case | in IC Ca++ occur over several b ea ts & in Post extra systolic potentia tion IC Ca++ | due to
a ccumula tion )
2. Sympathetic stimulation. via | Ca++ entry during p lateau O R via | Ca++ pump ac tivity in SR ( phosphola mbam )
3. Cardiac Glycoside ( Digitalis, Quabain ). ( digitalis Na+ - K+ ATPase  IC Na+ to |  Inhibition of Na+ Ca++ exc hange  | IC Ca++ )
Eventually all three | the IC Ca++ ÷ | contractility .

LENG TH TENSION RELATIO NSHIP :
* It describes the effect of ventricular cell length on the strength of contraction (similar in skeletal muscle).
* Pre loa d is equivalent to End Dia stolic Vol ( | end diastolic vol  | in fiber length  | in d eveloped tension )
* Afte rloa d is equivalent to Aortic Pre ssure . It | by | Aortic P. ( Velocity of contra c tion + b y | in after load )
Fig :








FRANK SRATLING RELATIO N SHIP : Is based on le ng th te nsion re la tion ship .
* Frank starling relation ship describes | in Cardiac output (stroke Vol) that occur in response to an | in venous P (end
diastolic Vol ).
In other word it is a mechanism that matches Cardiac output and venous return.
* Change in contractility shift Frank starling curve.
Fig:







VENTRIC ULAR PRESSURE - VO L LO O P :
* A cycle of ventricular contraction, ejection, relaxation, and refilling can be seen by combining of two curve into
Pressure - Vol loop . It is constructed by Diastolic and systolic Pressure curve.
Fig:








KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
25


C ARDIAC AND VASC ULAR FUNC TIONAL CURVE :
* Change in End diastolic is major mechanism of alteration in cardiac output.
* Cardiac functional curve shows frank starling relation ship for the ventricle.
* Venous return & vascular functional curve shows relation ship b/ w flow through the vascular sys & the right atrial P.
* Mean systemic P is equal right atrial P when there is no flow in CVS. It | or + by | or + in blood Vol.
* Slope of the venous return curve is determined by resistance of the vasculature.
* A clock wise relationship of venous return curve indicate + in TPR which results into | venous return and cardiac
output. Whereas counter clock wise relationship indicate | TPR ÷ | venous return & cardiac output.
| TPR ÷ + ve nous re turn to he a rt vs. + TPR ÷ | ve nous re turn to he a rt.
* When two curve intersects each other the point is called equilibrium or steady point.
* Equilibrium occur when cardiac output equals venous return.
* + Inotropic agent (digitalis) cause | in contractility → | in cardiac output which furthe r lowe rs rig ht a tria l P .
( this is exactly opposite of - ve Inotropic drug )
* | or + in Blood Vol ÷ | or + in venous return and cardiac output. It shows shift of curve.
Fig:









C ARDIAC O2 C O NSUMPTIO N : | by | afterload ,| size of heart, | contractility, | HR, ( rememb er after loa d is | by | aortic P)
C a rd ia c outp ut = stroke Vol × HR (can also b e measured by Flick's principle C O = O 2 c onsump tion / [O 2] p ulmona ry ve in - [O 2] p ul a rte ry)
Stroke Work = Stroke Vol × Aortic P
* Stroke work is work done by heart and fatty acid is primary source of energy for stroke work.

----------------------------------------------------------

REG ULATIO N O F ARTERIAL PRESSURE :
* FAST--- Neurally mediated, Baro receptor (stretch rec ep tor) respond fast and regulate minute to minute arterial BP.
* SLOW --- Renin angiotensin and Aldosterone respond slow.
* Baro receptor mechanism present in carotid sinus located near bifurcation of common carotid artery respond to
high or low BP. Additional baro receptor present in Aortic arch which respond only to | in arterial P. (but not to + BP)
* Baro receptor | the firing rate of carotid sinus nerve IX (glossopharyngea l) which carries information to vasomotor
center in brain.
* Set point for the mean arterial P in vasomotor center is 100 mmHg so if set point |, vasomotor center reduce it by |
parasym vagal out flow to heart and + sympathetic out flow to the heart and blood vessels (+ vasoconstriction).
* + Renal perfusion P ÷ Renin release ÷ Renin catalyze angiotensinogen to angiotensin I (in plasma) than
angiotensin I is converted to ATII (in lung) by ACE.
* AT II ÷ vasoconstriction of arterioles (|TPR) & stimulates Aldosterone secretion. (|K+ & + b lood vol also stimula te Aldosterone
secretion )
* Aldosterone ÷ Reabsorption of salt and water by distal tubules ÷ | blood Vol and mean arterial P.

O THER REG ULATIO N O F ARTERIAL BLO O D PRESSURE :
1. C e re b ra l Isc he mia - - | both parasympathetic & sympathetic outflow. (tha t is why is very hard to control BP in CVA or strokes)
Mean arterial P | to life threatening level.
Flow to other organ (eg kidney) significantly reduced ÷| Renin, | ATII ÷ | TPR.
* C ushing re a c tion - - | in IC Pressure ÷ compression of cerebral blood vessel ÷ cerebral ischemia ÷ | sympathetic
out flow ÷| contractility, | TPR with simultaneous reduction in Heart rate (Parasym).
2. C he more c e p tor in a ortic a nd c a rotid b od ie s are very sensitive to hypoxia (because of very high ra te of O2 consump tion) ÷
stimulate vasomotor center to restore BP.
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
26


3. Va sop re ssin ( ADH) release in response to + blood Vol or P.
ADH a c t on --- V1 re c e p tors ÷ cause vasoconstriction (| TPR)
V2 re c e p tors ÷ | reabsorption of water by distal tubule and collecting duct.
4. Atria l na triure tic Pa ptide ( ANP) release in response to | atrial P ÷ dilation of arterioles (inhibit vasoconstric tion), & + TPR. It
also | salt & water excretion and inhibit Renin release.

-------------------------------------------------------------------

* Flow through capillaries is regulated by contraction and relaxation of the arterioles and the precapillaries sphincters.
Remember capillaries do not have smooth muscles instead containing endothelial cells.
* BBB is a tight cleft b/ w endothelial cells of capillaries. In intestine & liver these cell clefts are wide open called
Sinosoid s it allow protein to cross. ( 3 types of subs cross capillary wall 1. lipid soluble subs. 2. sma ll water soluble subs. 3. large wa ter
soluble subs via pinocytosis. )

FLUID EXCHANG E AC ROSS C APILLARIES :
* It can be determined by Starling equation Jv = K] [ ( Pc - Pi ) - ( tc - ti ) ] Jv is fluid flow and Kf is filtra tion coefficient
Pc (Capillaries hydrosta tic P) when | it cause net filtration. Pc is hig he r a t a rte riola r e nd of the capillaries than venous end.
Exc e pt in glomerular capillaries where it is nearly constant. ( Rememb er | arteriolar or venous P ÷ | Pc but | venous P has grea ter
effec t on Pc )
Pi ( Interstitia l fluid hydrosta tic P) Normal Pi is 0mmHg . | in Pi oppose filtration out of the capillaries.
tc ( Capillaries oncotic or colloid osmotic P) when | opposes filtration out of capillaries.
ti ( Interstitia l oncotic or colloid osmotic P) when | favor filtration out of capillaries.
Fa c tor tha t inc re a se filtra tion a re | Pc, +Pi. +tc, |ti .

--------------------------------------------------------------------

FUNCTIO N O F LYMPHNO DE:
* Excess filtered fluid is returned to circulation via lymph. One way flap valve permit unidirectional lymph flow.
Skeletal muscle contraction also aid it.
* Edema caused by excess filtration or blocked lymphatics or by | Pc, + tc, | K]. (K] | due to burn & inflamma tion)
* EDRF (produce by endothelial c ell) relaxes smooth muscle by Guanylate cyclase mech produce GMP. ( one form of EDRF is
Nitricoxide )
* Ach ÷ vasodialation by stimulation of EDRF production.
-------------------------------------------------------------------

SPEC IAL C IRC ULATIO N :Blood flow is regula ted by a ltering arteriolar resista nc e, can b e varied depends upon metabolic need.
Autoc irc ula tion - - When perfusion P | ÷ arteriolar smooth musc le stretc hes follow by contrac tion ÷ vasoconstric tion oc c ur (by this maintain
constant flow)
Ac tive Hype re mia - - Is blood flow to organ proportiona l to its metabolic need . eg . Heart
Re a c tive Hyp e re mia - - Is | in blood flow to an organ after a period of oc clusion to flow. eg . Heart
Va sod ila tor me ta b olite s are CO2, H+, K+, lactate and Adenosine.
-------------------------------------------------------------------

VASO ACTIVE HO RM ONES :
* Hista mine ÷ arteriolar dilation & venoconstriction. It | Pc & cause local edema. (Wheal is an ed ema results from local
hista mine release).
* Bra d ykinine ÷ arteriolar dilation and venous constriction it also cause edema.
* Se rotinin ÷ arteriolar vasoconstriction. It release upon vessel damage and prevent blood loss.
* Prosta g la nd ins --- PGI2 (prostac yc lin) and PGE ÷ vasodilation
PGF ÷ va soc onstric tion
TxA2 ÷ va soc onstric tion

C O RO NARY ARTERY C IRCULATIO N : 5% is resting cardiac output.
* Control by local metabolites specially hypoxia and Adenosine ÷ vasodilatation to | blood flow.
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
27


* Exhibit Autoregulation, active and reactive hyperemia.
* During systole mechanical compression of the coronary vessel reduces blood flow, Reactive hyperemia occurs after
that brief period of occlusion to replay the O2 dept. (Mechanical Effect)
* Sympathetic nerev play a minor role.

C EREBRAL CIRC ULATIO N : Is 15 % of resting cardiac out put.
* Control by local metabolites specially CO2 ÷ ↑ or ↓ of pH ÷ vasodilatation of cerebral arteries to | blood flow.
* Vasoactive subs in general circulation have little or no effect on cerebral circulation because of BBB.

SKELETAL M USC LE C IRC ULATIO N : Is 20 % of resting cardiac out put.
* At rest symp control of blood flow predominate where as during exersize local metabolites control over rides
sympathetic control.
* Local metabolites like lactate, Adenosine, K+, dilates vessel and increase blood flow.
* Mechanical effects compensate by reactive hyperemia. (due to temporary compression of arterioles with resultant
vasodilata tion )
* o receptors cause vasoconstriction where as | receptors cause vasodialation.

SKIN C IRC ULATIO N : Is 5 % of resting cardiac output.
* Skin have extensive sympathetic innervation and flow of blood is in extrinsic control (temperature regulation).

PULM O NARY CIRC ULATIO N : Is 100% of cardiac out put. Local metabolites are most imp mechanism.

RENAL C IRC ULATIO N : Is 25% of resting cardiac out put.
-----------------------------------------------------------------

* Upon Standing (gravity) ÷ | in venous P, | Pc ÷ | Filtra tion ÷ initial + in stroke vol & cardiac output ÷ comp ensa tory mec h starts (via carotid
baro rec ep tors) ÷ HR |, TPR | ÷ BP return to norma l BP.
* On Exercising ÷ HR |, stroke vol |, cardiac output |, Arterial P | (slightly), Pulse P | (due to | stroke vol), TPR + (due to vasodilata tion of skeletal m
bed), Arterio venous O2 differenc e | ( due to increase O2 consump tion).
* On Hemorrhage ÷ HR |, TPR ,| contrac tility |, unstressed vol + (stress vol |), Renin |, ATII |, Aldosterone |, EN & norEN |, ADH |. ( Rememb er
vaso constric tion occ ur in skeleta l, splanchnic & cuta neous vascular b ed; but it does not oc cur in coronary and cerebral va scular b ed because
to ensure maintained blood flow to heart and brain ).
----------------------------------------------------------------------------------

* Blip is aortic P tracing occur following closure of aortic valve also called dicrotic notch or Incisura.
* Rapid flow of blood from atria to ventricle cause 3rd heart sound (normal in c hildren but associated with dis in adults).
* Inspiration split the second heart sound.
* Ventricle filling is divided into Rapid ventricle filling & Reduced ventricle filling (Diastasis) which is last part of ventricle
filling curve.

NEURO PHYSIO LO G Y
* Autonomic nervous sys (symp, parasymp & enteric) is distinct from Somatic nervous sys which innervate skeletal muscles
and use ACh as a NTwhere as receptor is nicotinic.
* Symp neurotransmitter is norEN in effector organ except in sweat glands where it is ACh and receptors are
muscarinic.
* Parasym and Symp receptors in ganglion are Nicotinic and NTis ACh.
* Symp ganglia are located in paravertebral chain where as parasymp ganglia are located in effector organ.
* Preganglionic symp fiber are short and synapse in autonomic (paravertebra l) ganglia its cell bodies are present in CNS
& Postganglionic symp fibers are long & synapse in effector organ & its cell bodies are located in Autonomic
(paravertebral) ganglia.
* Preganglionic parasymp fibers are long and synapse in autonomic ganglion in effector organ it cell bodies are
present in CNS & postganglionic parasym fibers are short & synapse on effector organ, its cell bodies are present in
autonomic ganglion.
* Parasymp receptor in effector organ is Muscarinic but in skeletal muscle (somatic) is Nicotinic.
* Adrenal medulla is a special case in which preganglionic fiber syna p se d ire c tly on c hroma ffin c e lls of adrenal
medulla it use ACh as NT& secret EN 80% & norEN 20% . (because rememb er preganglionic fibers norma lly synapse on ganglion).
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
28


ADRENERG IC RECEPTO R TYPES :
1. o1 - located on smooth muscle except bronchial smooth muscle ÷ Exc ita tion ( via IP3 me c h) & is equally sensitive to
EN & norEN.
2. o2 - located on smooth muscles, Presynaptic nerve terminal, platelets and fat cells ÷ Inhib ition ( via c AM P ma c h) .
3. |1 - located in heart, kidney and fat cells ÷ Exc ita tion ( via c AM P ma c h) .
4. |2 - located on vascular, bronchial and GI smooth muscles ÷ Re la xa tion ( via c AM P ma c h) and is more sensitive to EN
than norEN and more sensitive to EN than o receptors.
* When sma ll a mount of EN release from adrenal medulla cause vasodilation but when large a mount of EN release from adrenal medulla for eg as
in pheochromocytoma results into vasoconstric tion (via o rec ep tors).

* o1 --- constrict pupil. whe re a s |1 --- heart contraction, | renin secretion, and lipolysis in fat cells.
* In sweat gland sympathetic action ÷ | sweating but neurotransmitter is ACh and receptors are muscarinic.

C HO LINERG IC RECEPTO R TYPE :
1. Nic otnic re c e p tors (ac tivated by ACh or Nicotine) are located in autonomic ganglia & neuromuscular junction ÷
Excitation ( nic otinic or Ac h re c e p tors a re ion c ha nne l for Na + a nd K+ ) . Ganglion blockers ( He xa m e thonium , Trime thp p ha n ) block
nicotinic receptor for Ach in autonomic ganglia but not at neuromuscular junction ( b e c a use re c e p tors a re not id e ntic a l) .
2. M usc ura nic re c e p tors located on
* In Heart M2 receptors are located on SA node ÷ Inhibition ( via c AM P) by + the rate of spontaneous depolarization.
* In Glands ÷ Exitation ( via IP3)
* In Smooth muscle ÷ Excitation ( via IP3) with resultant constriction of bronchial smooth muscle, contract bladder wall
& relax sphincter, | GI motility and relax sphincter. ( note : in va sc ula r smo oth musc le M re c e p tors c a use re la xa tion or va sod ila tion)
---------------------------------------------------------------------------------------

SENSO RY SYSTEM :
A. Typ e of se nsory tra nsd uc e r :
1. Mechano Receptors -- * Pacinian Corpuscles (encod e vibration and tapping) & adop t rapidly
* Meissners corpuscles present on non hairy skin (encod e velocity) & adopt rapidly
* Merkels disc ( loca tion ) & adop t slowly * Ruffini,s corpuscles (encode pressure) & adopt slowly
* Joints, stretch rec ep tors in muscles * Hair cell in auditory and vestibular system.
2. Photo Receptors ------------- Rods and Cones of the retina.
3. Chemo Receptors ----------- Olfactory Receptors, taste receptors, osmo receptors and Carotid body Receptors.
4. Temp & Pain Receptors ---- Noci Receptors.
(Pacinian vibrates meissners run (velocity) to merkel loca tion and shares ruffini's pressure)

B. Fib e r type a nd ve loc ity :
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
G e ne ra l Fib e r Typ e Se nsory Fib e r Typ e Dia m e te r C ond uc tion Ve lo c ity
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
A - Alp ha (large o motoneuron) Extrafusal fiber I a (musc le spindle afferent) Largest Fastest
I b (golgi tendon organ) Largest Fastest
A - Beta ( Touch & Pressure) II Sec Afferent of musc le spindle touch & pressure Medium Medium
A - Ga mma (¸ motoneuron to musc le spindle) Intrafusal fiber Medium Medium
A - Delta (touch, pressure, temp, pain) III Touch, Pressure, Temp & Fast Pain Sma ll Medium
B Preganglionic Autonomic Fiber Sma ll Medium
C Slow Pain, Postga nglionic Autonomic Fiber IV Pain, Temp (unmyelina ted) Smallest Slowest
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* Receptive Field in the region that contain sensory transducer can be excitatory or inhibitory.

STEP IN SENSO RY TRANSDUCTIO N : Stimulus arrives in sensory receptors ÷ opening of ion channel in sensory receptor
÷ inward current cause depolarization ( except in photo receptors where light cause hyper polarization).
* Action potential is fired only when stimulus to receptor potential is large enough to exceed threshold.

ADO PTATIO N O F SENSO RY RECEPTO R :
1. Slow adopting receptor eg. musc le sp ind le , p re ssure , slow p a in. Respond relatively to prolong stimulus.
2. Rapidly adopting receptor eg. p a c inia n c orp usc le s, lig ht touc h respond fast but show decline in action potential
frequency with time in response to constant stimulus.
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
29


SENSO RY PATHWAY :
a. 1
st
order neuron --- Primary afferent neuron receive signals. These cell bodies are located in dorsal root ganglia and
CN ganglia.
b. 2
nd
order neuron --- Located in spinal cord & brain stem. Receive information from primary afferent neuron & send
it to thalamus.
c. 3
rd
order neuron --- Located in sensory nucleus of thalamus from here it send information to cerebral cortex.
d. 4
t h
order neuron --- Located in cortex and result in conscious perception of stimulus.
--------------------------------------------------------------------------------------------

PATHWAY O F SO MATO SENSO RY SYSTEM :
1. Dorsa l C olumn Syste m: * Consist of group II fiber which run in the Dorsal Root; it asc end ipsila terally to the Nuc Gra cilis & Cunea tus of
(Posterior column sys) medulla from here 2
nd
ord er neuron cross the mid line and ascend to the contrala teral thala mus.
* Dorsal column system process sensa tion of touc h, p re ssure , vib ra tion, a nd mo ve me nt.
2. Ante rola te ra l Syste m: * Consist of group III and IV fibers which enter the spinal cord and termina te in the dorsal horn. Form here 2nd ord er
neuron sensory projec t across the midline to the Anterola teral quadrant & asc end to the contra la tera l thala mus.
* Anterola teral system proc ess sensa tion of te mp a nd p a in.

* Destruction of thalamic nuclei result in loss of sensation on the contra lateral side of the body.

SO M ATO SENSO RY C O RTEX :- * Major somatosensory area of cortex is S I and S II. S I have somatotropic representation
similar to thalamus. This map of body is called Homunculus (HAL).
PAIN: * Perceive by Noci receptors which are free nerve ending and neurotransmitter is Substance P (opiate inhibit it).
* Fa st p a in fib e rs are g roup III fib e rs shows rapid onset and offset and is loc a lize d .
* Slow p a in fibe rs are C, ( IV) fib e rs perceive aching, burnig, throbbing sensation and is poorly loc a lize d .
------------------------------------------------------------------------------------------

VISIO N :
* Refractory power of lens is measured by Diopters. 10 Diopters = 10 cm
* Emme trop ia -- Normal -- light focus on retina.
* Hyp e rop ia - - Farsightedness -- Light focus behind the retina (convex lens).
* M yop ia - - Nearsightedness -- Light focus in front of retina (Biconcave lens).
* Astig ma tism -- Curvature of lens is not uniform (cylindrical lens).
* Pre sb yop ia - - Loss of accomodation of lens with aging. The near point appear more farther from eye (convex lens).

* Receptor cells are Rod and Cones which are not present at Optic disc and create a blind spot.
* Fe w c one s syna p se on sing le Bip ola r C e ll whic h further synap se on single Ganglion Cell ÷ this arrangement cause hig h a c uity & lo w se nsitivity.
* M a ny Rod s syna p se on sing le b ip ola r c e ll which results into le ss a c uity & g re a te r se nsitivity . (because many rods can ac tiva te single bipolar c ell).
* In FOVEA where acuity is high Cone Bipolar ratio is 1:1 .
* Horizontal and Amacrine Cell form local circuit with Bipolar Cell.
* Axon of the Ganglion form Optic Nerve & Optic Tract terminate in the Lateral Geniculate Body of the thalamus.
* Fiber from Lateral Geniculate Body form Geniculocalcarine Tract and pass to cortex of Occipital lobe.
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
FUNC TIO N RO DS C O NES
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Se nsitivity to lig ht Sensitive to low intensity to light ( Night vision ) Sensitive to high intensity light ( Day vision )
Ac uity Low visual ac uity ( not present in FOVEA ) High visual Acuity ( Present in FOVEA )
Da rk Ad a p ta tion Rod adopt la ter Cones adop t first
C olor vision NO NO
M ore a t p e rip he ra l of re tina YES YES
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* Cutting the Optic nerve ÷ Blindness of ipsilateral eye.
* Cutting the Optic chiasm ÷ Hetronymous Bitemporal Hemianopsia.
* Cutting the Optic Tract ÷ Homonymous Contralateral Hemianopsia.
* Cutting the Geniculocalcarine Tract ÷ Homonymous Hemianopsia with Macular sparing.
* Cutting unilateral temporal lobe radiation ÷ Homonymous Quadrantopia (pie in the sky)
* Bilateral visual cortex lesion ÷ Macular sparing.

KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
30


Photo Re c e p tion of Rod s:
* In Rod Photosensitive element is Rhodopsin composed of Scotopsin & Retinine ( Aldehyd e of vit A ) . Vit A deficiency
cause night blindness. (because Vit A is essentia l for regenera tion of Rhodopsin).
* Lig ht on re tina c onve rt 11- c is Rod op sin ÷ All tra nsRod op sin ÷ M e ta Rod op sin I I ( a c tive form) ÷ tha n M e ta rod op sin II a c tiva te s G p rote in c a lle d
Tra nsd uc in whic h in turn a c tiva te Phosp hod ie ste ra se ÷ Phosp hod ie stra se furthe r c a ta ly ze c onve rsion o f c G M P into 5‘ G M P ( c G M P le ve l +) . Tha n
+ c G M P re sults into c losure of Na + c ha nne l & Hyp e rp ola riza tio n of the c e ll M e mb ra ne . ( | lig ht c a use | d e g re e of hyp e rp ola riza tion ) .
* Excitatory NThyperpolarize bipolar & horizontal cell in response to light. vs.
Inhibitory NTdepolarize it in response to light.

Re c e ptive visua l Fie ld :
* Light hit the centre of receptive field & depolarize (excite) the Ganglion cells & constitute On Center Off Surround
receptive visual field pattern. (On Center Off surround is another possible pattern in which light hits the surround of
receptive field & hyperpolarize (inhibit) the ganglion cell)
* Lat Geniculate Cell of the Thalamus retained the Center - Surround ON - OFF pattern transmitted from Ganglion cell.

REC EPTIVE FIELD O F VISUAL CO RTEX : Detects shape and orientation of figure. Visual Cortex comprise of three Layers.
1. Simple Cells (have c enter -surround On - Off pa ttern & are elonga ted Rods) --- Respond to Bars of light with correct position &
Orientation.
2. Complex Cells --- Respond best to moving Bars and edge of light.
3. Hyper Complex Cells --- Respond best to lines with Particular Length and to curve and angles.
--------------------------------------------------------------------------------------------------------------------

AUDITO N :
* Frequency measure in Hertz where as Intensity in Decibles.
Fig:






* Middle ear is air filled where as inner ear is fluid filled.
* M id d le e a r contain Tympanic mem, Ossic les (malleus, incus, stapes) and Oval window where as Inne r e a r consist of Bony lab yrinth (semicirc ular
canal,
cochlea, vestibule) and series of Duc ts called Membranous labyrinth whic h contain endolymp h (inside the duc t) and perilymph (out sid e the
duc t).
* Sound c a use Tymp a nic me m to vib ra te , in turn Ossic le vib ra te a nd p ushe s the sta p e s in to the Ova l Wind ow ( a
me m
b / w inne r e a r a nd midd le e a r ) whic h d isp la c e s the fluid in the inne r e a r.
* Sound energy is amplified by lever action of Ossicles and send conc of sound wave from Tympanic mem to Oval
Window.

C O CHLEA consist of three Tubular canals.
1. Scala Vestibuli --- Contain perilymph and is | in Na+.
2. Scala Tympani --- Contain Perilymph and is | in Na+.
3. Scala Media --- Contain endolymph and is | in K+* ( Scala Media is Bordered b y Basilar Mem the site of Organ of Corti ).

Fig:







KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
31


O RG AN O F C O RTI is located on Basilar mem. Its Receptors are inner Hair cells (in single row) & outer Hair cells (in parallel
row) Outer Hair cells are greater in number than inner Hair cells.
* Cilia protrudes from Hair cells and imbedded into Tectorial mem .
* Spiral Ganglion contain cell bodies of CN VIII which synapse on Hair cells.
* Sound wave vibrates Organ of Corti ÷ Basilar mem to vibrate & push against Tectorial mem ÷ Hair cells to bend ÷
bending of cilia (which cause change in K+ conduc ta nc e) ÷ Depolarization ÷ Ossillating potential results. (bending in other
direc tion cause hyp erpolarization)
* Ossillating Potential (Cochlear microphonic potential) of Hair cell ÷ intermittent firing of Choclear nerve.

ENC O DING O F SOUND WAVE :
* Base of the Basilar mem ( near Oval and Round window ) is narrow and stiff it respond best to high Frequency.
* Apex of the Basilar mem ( near Helicotrema ) is wide and compliant it respond best to low Frequency.

C ENTRAL AUDITO RY PATHWAY :
* C oc hle a r ne rve Fib e r a sc e nd throug h La te ra l La minisc us ÷ Infe rior C ollic ulus ÷ M id d le G e nic ula te nuc le us of tha la mus ÷ a ud itory C orte x.
* Fiber may crossed or uncrossed that’ s why lesion of the chochlea of one ear cause unilateral deafness where as
more central
unilateral lesion does not cause complete unilateral deafness.
* Ability to recognize a patterned sequence is a property of Cerebral Cortex.
* Remember always Medial geniculate to Ear and lateral geniculate to Eye.

VESTIBULAR SYSTEM :
* Vestibular organ is a membranous labyrinth consisting of three perpandicular canal filled with Endolymph.
1. Semicircular canal --- De te c t a ng ula r a c c e le ra tion a nd rota tion.
2. Utricle --- De te c t line a r a c c e le ra tion.
3. Saccule --- Also de te c t Line a r a c c e le ra tion .

* The vestibular receptor cells are Hair cells located at the end of each semicircular canal.
* Vestibular Hair cells are embedded in gelatinous substance called C a p ula .
* Kinoc ilium is a single long cilium where as Ste re oc ilia are small cilium.
* If Sterocilium b ends toward the Kinocilium ÷ Hair c ells Depola rize whe re a s If Sterocilium bends away from Kinocilium ÷ Hair cells Hyperpolarize.
* During initial counterclockwise rotation Left Horizontal canal is excited & Right Horizontal canal is inhibited but after
few seconds endolymph catches up the movement of head & capula; cilia return to their upright position.(no more
hyperpolariza tion or d epolariza tion)
* When head sud d e nly stop s endolymph continues to move to counterclockwise for a while (cause cilia to move in opp
direc tion) if the hair cell was depolarized with initial movement, it will now hyperpolarized and hyperpolarized one
will depolarize.

* Ve stib ula r - O c c ula r Re fle x :
Nysta g mus --- An initial rotation of head cause eye to move slowly in opposite direction when limit of eye
movement reaches the eye rapidly snap back than move slowly again. (nystagmus in rest arise from disruption in c entra l or
peripheral vesticular connec tion)
Post rota tory nysta g mus --- Occur in the opposite direction of head Rotation.
-----------------------------------------------------------------------------

O LFAC TO RY receptor cells are present on epithelia and are true neurons. It conduct action potential to CNS via CN I.
* These neuron are the only eg. in nervous system that turn over and replace neuron.
* CN I carries information from receptor cell to Olfactory bulb, the Axon of olfactory nerve is unmyelinated C fiber
and are smallest therefore slowest.
* Olfactory epithelium is a lso inne rva te d b y trig e mina l ne rve V which detect Noxious stimulus such as Amonia.
* Olfactory nerve passes through the Cribriform plate to Olfactory bulb, its fracture ÷ Hypoosmia, Anosmia.( CN V
response is inta c t )
* Mitral cells in the Olfactory bulb are 2
nd
order neurons from Olfactory Tract and project to Prepiriform Cortex.
* Odorant molecules bind to the olfactory receptor neuron ÷ activate G protein ÷ activates adenylate cyclase ÷ |
cAMP ÷ Open Na+ channel ÷ depolarization of receptor potential ÷ Fire action potential.
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
32


TASTE :
* Taste buds are located on special Papillae & are covered with micro villi. ( taste rec ep tors are present on taste bud )
* Ant 2/ 3 of tongue has Fungiform Papillae ÷ detect salty and sweety sensation and is innervated by Facial nerve VII.
* Post 1/ 3 has Circum vallate & Folliate papillae ÷ detect sour & bitter sensation & is innervated by Glossopharyngeal
nerve IX.
* Back of throat and Epiglottis is innervated by vagus nerve X.
* CN VII, IX, X enter the medulla ascend in solitary tract where 2
nd
order neuron terminates in solitary nucleus; from
here itproject primarily ipsilaterally to ventral posteromedial nuc of thalamus ÷ taste cortex (which is present in the ventra l
region of Post central gyrus).
--------------------------------------------------------------------------
M O TO R SYSTEM :-
* Motor unit is a single motoneuron plus muscle fiber that it innervates. (single motoneuron may innervate few musc le for fine
movement & many musc le for large movement) .
* Motone uron p ool is a group of neuron that innervates fibers with in same muscle.
* Force muscle contraction is graded by recruitment of additional motor unit ( size p rinc ip le ) .
* Sma ll motone uron -- innervate few muscle fibers, has lowe r thre shold therefore fire first and generate small force.
* La rg e motone uron -- innervate many muscle fibers, has hig he st thre shold and therefore fire last and generate large
force.
-------------------------------------------------------------------------
M USC LE SENSO RS :- 4 Types of muscle sensors
1. Muscle spindle Ia has parallel arrangement with extrafusal muscle fiber, detect both static & dynamic changes in
muscle
length.
2. Golgi tendon organ Ib has serial arrangement with extrafusal muscle fiber detect muscle tension.
3. Pacinian Corpuscles II detect vibration.
4. Free nerve ending III, IV detect noxious stimuli.
TYPE O F M USC LE FIBER :-
1. Extra fusa l fibe r -- make muscle bulk and stimulate by o motoneuron. It p rovid e forc e of muscle contraction.
2. Intra fusa l fib e r -- are smaller than extrafusal fiber. It e nc a p sula te d to form musc le sp ind le & run parallel to extrafusal
fiber but do not run entire muscle length.

Intrafusal Fiber
.\
Ia typ e afferent ÷ musc le strength (d yna mic c ha ng e s) ÷ Nuc b a g fib e r Nuc c ha in fib e r ÷ musc le c hange (sta tic c ha ng e ) ÷ II type a fferent

-------------------------------------------------------------------------
* Muscle spindle -- Finer movement need greater no of muscle spindle in muscle. (muscle spindle consist of intra & extra fusal
muscle fiber)
* There are two type of intrafusal fiber present in muscle spindle.
1. Nuc le a r Ba g fib e r: Detect Dyna mic c ha ng e s (rate & change in musc le strength a t motion) & is Innervated by Ia a ffe re nt.
2. Nuc le a r C ha in fib e r: Detect Sta tic c ha ng e (a t rest) in the muscle length & is innervated by group II a ffe re nt.

FUNCTIO N O F MUSC LE SPINDLE : Muscle spindle opposes over stretching of muscle by contracting it.
* Stretched muscle further stretches Muscle spindle ÷ Stimulate Ia (velocity) & group II (static) afferent fibers ÷
stimulate o motoneuron in spinalcord ÷ contraction.
Func tion of ¸ Motone uron :- ¸ Motoneuron Innervate intrafusal muscle fiber it adjust the sensitivity of muscle spindle. o
& ¸ motoneuron are coactivated so muscle spindle remain sensitive to change in muscle length during contraction.

M USC LE REFLEXES
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------
REFLEX NO O F SYNAPSE STIM ULUS AFFERENT FIBER RESPO NSE
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Stretc h Reflex ( Knee Jerk ) Monosynsp tic Stretch Musc les Ia Muscle contra c tion
Golgi Tendon Reflex ( Clasp Knife ) Disynaptic Contra c t musc le Ib Musc le Relaxa tion
Flexion withdrawal Reflex Polysynap tic Pain II, III, IV Ipsila tera l Flexion & contrala teral
( after touching Hot objec t ) Extension
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
33


Stre tc h Re fle x -- Ia afferent synapse on o motoneuron to cause contraction in the muscle that was stretched.
( | ¸ motor a c tivity ÷ | the sensitivity of muscle spindle whic h result into exaggera ted stretch reflex ).
G olg i te nd on Re fle x - - Activated muscle contraction stimulate Ib afferent fiber of Golgi tendon ÷ than Ib inhibit
interneuron in spinal cord which further inhibit o motoneuron ÷ Relaxation of muscle that was
originally contracted.
C la sp Knife re fle x is an exaggerated form of the Golgi tendon ref it can occur in Corticospinal tract dis → ( sp a stic ity ) .
Fle xion withd ra wa l re fle x -- After touching a hot object pain stimulus from II, III, and IV afferent fiber cause ipsilateral
Flexion and contralateral extension ( c ross e xte nsion re fle x ) to maintain balance. After
discharge does not allow the muscle to relax for some time because of persistent neuronal
activity in polysynaptic circuit.
---------------------------------------------------------------

SPINAL O RG ANIZATIO N O F M O TO R SYSTEM :
1. C onve rg e nc e is when more than one muscle spindle stimulates single motoneuron ( Ia afferent ) produce sp a tia l
Summa tion ( more tha n one input bring musc le to threshold ) & te mpora l summa tion ( input arrive rapid succ ession ).
2. Dive rge nc e is when Ia afferent (muscle spind le) project to more than one or all motoneuron of the homonymous mus.
3. Re c urre nt inhib ition ( Re nsha w c e lls) : Renshaw cells are inhib itory ne uron it inhibit motoneuron (- ve feed back ) in
ventral horn of spinalcord. It receives input from collateral axons of motoneuron.
---------------------------------------------------------------

BRAIN STEM C O NTRO L O F PO STURE : Motor center and Pathway are of two types,
1. Pyra mid a l Tra c t -- is Corticospinal & Corticobulbar Tract. Both Pass through medullary pyramids.
2. Extra p yra mid a l Tra c t -- are all other pathway.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

EXTRAPYRAM IDAL TRACTS AND ITS O RIG INS :
1. Rub ro sp ina l Tra c t - - Origina te in re d nuc & projec t interneuron to la tera l spinalcord. It stimula te fle xors & inhib it e xte nsor.
2. La te ra l Ve stib ulosp ina l Tra c t -- Origina te in Die te r’s nuc & projec t to Ipsila tera l motoneuron & interneuron. It stimula te e xte nsors & inhib it fle xors.
3. Pontine Re tic ulosp ina l Tra c t -- Origina te in nuc in p ons & projec t to Ventromedial spinalcord. It stimula te b oth e xte nsors & fle xors.(but more Ext)
4. M e d ulla ry re tic ulosp ina l Tra c t -- Origina te in me d ulla ry Re tic ula r forma tion & projec t to spinalcord. It inhib it b oth e xte nsor & fle xor. (b ut more ext)
5. Ta c tosp ina l Tra c t -- Origina te in sup e rior c ollic ulus & projec t t o cervical spinal cord. It c ontrol ne c k musc le s.
EFFECT O F TRANSECTIO N O F SPINAL C O RD :
1. Pa ra p le g ia (Loss of voluntary movement) below the level of lesion.
2. Loss of c onsc ious se nsa tion below the level of lesion.
3. Initia l loss of re fle xe s (spinal shock) flaccidity occur below the level of lesion due to loss of o & ¸ motoneuron.
( with time partial recovery and return of reflexes or even hyperreflexia will occ ur )

* C7 le sion results into loss of sympathetic tone to the heart ÷ + HR & + BP .
* C3 le sion will stops breathing because respiratory muscle disconnected from brain stem Control center.
* C1 le sion cause Sudden death eg. as in hanging.

EFFECT O F TRANSECTIO N ABO VE THE SPINAL C O RD :
* Le sion a b ove La te ra l Ve stib ula r Nuc le us - - remove inhibition from higher center and cause excitation of o and ¸
Motoneuron ÷ De c e re b ra te rig id ity (rigid posture).
* Le sion a b ove Pontine Re tic ula r forma tion - - removal of inhibition from pontine reticular formation & resultant
excitation of o & ¸ motoneuron & cause De c e re b ra te rig idity (rigid posture)
* Le sion a b ove the Re d Nuc le us ÷ results in De c ortic a te Posturing and inta c t tonic ne c k re fle x.
-----------------------------------------------------------------------

C EREBELLUM :- Central control of movement.
FUNCTIONS --- 1. Control of Balance an eye movement conduct by Ve stib ulo Ce re be llum.
2. Planning and Iniciation of movement control by Ponto C e re b e llum.
3. Synergy (Control of ra te, Forc e, Range and Direc tion of movement) control by Sp ino Ce re b e llum.


KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
34


La ye rs of c e re be lla r c orte x :
1. G ra nula r La ye r ( inner most ) -- contain granule c ells, Golgi II cells & Glomeruli. ( In glomeruli axons of mossy fibers form syna pse on granular &
golgi II cells ).
2. Pe rkinji C e ll La ye r ( middle layer ) -- out p ut is a lwa ys inhib itory.
3. M ole c ula r La y e r ( outer la yer ) -- contain Stella te & Basket c ells, Dendrites of perkinji & golgi type II c ells & parallel fib ers (axons of granule cells).

C onne c tion of Ce re b e lla r Corte x :
* Inp ut of c e re b e lla r c orte x :
1. C limb ing Fib e rs - Play role in c e re b ra l motor le a rning . It originate in infe rior O live (medulla) make multiple synapse
on perkinji cells results in c omp le x Sp ike s.
2. M ossy Fibe rs - Originate in brain stem & spinalcord. It synapse on perkinji fibers (via interneuron) & on glomerular
Complex. M ossy fib e r g ive rise to p a ra lle l fib e r ÷ e xc ite multip le p e rkinji c e lls a s we ll a s inhib itory ne uron ÷ inhib ition.

O ut p ut of c e re be lla r c orte x :
* The only out put from cerebellar cortex are perkinji cells and is always inhibitory (neurotransmitter is GABA)
* Inhibitory out put project to deep cerebellar nuclei and vestibular nuclei. It regulates synergy.

Disord e r of C e re b e llum ( Ata xia ) :
La c k of c oord ina tion: (Poor execution & delayed inhibition of movement), Inability to perform rapid alternating movement
called Dysdiadochokinesia.
Inte nsion tre me r occur during voluntary movement.
Re b ound Phe nome non - inability to stop movement.
------------------------------------------------------------------------

BASAL G ANG LIA :- Control of movement
* Basal ganglia p la n a nd e xe c ute smooth move me nt by modulating thalamic out flow to motor cortex. Many of its
synaptic connection are inhibitory and use GABA. (Its lesion results into loss of GABA)

Ba sa l G a ng lia c onsist of :-
1. G lob us p a llid us Lesion ÷ Ina b ility to ma inta in p ostura l sup p ort and a the tosis (involuntary slow movement of hand & foot).
2. Sub Tha la mic Nuc le us Lesion ÷ Wild flinging movement called He mib a llismus. (ca used b y release of inhibition on
contra la tera l side)
3. Stra itum Lesion ÷ Q uic k c ontinuous unc ontrolla b le move me nt as in Huntington. (caused b y release of inhibition)
4. Puta me n Lesion ÷ involuntary purposeless muscular movement called C hore a .
5. Sub sta ntia Ne g ra Lesion ÷ Destruction of Dopaminergic neuron ÷ O ve r re a c tivity of inhib itory p a thwa y of Stra itum
& Glob us p a llid us ÷ Lead pipe rigidity, resting tremor & reduced voluntary movement ( Pa rkinson Dis) .

M O TO R C O RTEX :-
1. Pre motor C orte x & Supp le me nta ry M otor Corte x ( a re a 6 ) generate a p la n for move me nt .
* It is active during Mental Rehearsal for movement which than transfer to primary motor cortex for execution.

2. Prima ry M otor C orte x ( a re a 4 ) is responsible for e xe c ution of move me nt.
* Epileptic event in Primary motor cortex ÷ Jacksonian Siezures.
* Homunculus is upside down Representation of the Human Body in cerebral cortex.
--------------------------------------------------------------------------



HIGHER FUNCTIO N O F CEREBRAL C O RTEX :-
1. EEG Find ing s :
* EEG wave consist of alternating excitatory & inhibitory synaptic potential in the pyramidal cell of the cerebral
cortex.
* EEG change occur due to cortical evoked potential. In alert adult | waves predominate & Upon relaxation o
waves predominate where as during sleep slow waves predominate.

KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
35


2. SLEEP :
* Sleep wake cycle occur in c irc a d ia n rhythm which resides in Sup ra c hia sma tic nuc le us of hypotha la mus, which
receives input from retina.
* Rapid eye movement sleep occur every 90 min. During REM sleep EEG resembles that of awake person. Most
dream occur during REM sleep. | age and Benzodiazepine ÷ + in REM sleep.
* Slow wave sleep is Dream less Sleep ( dream do occur but cant be remmember ).

3. LANGUAG E :-
* Left hemisphere is usually dminant with respect to language even in left handed person. Its lesion ÷ Aphasia.
* Right hemisphere is more dominant in Facial expression, Intonation (voice tone), Body language, and Spatial task.
* Damage to We rnic ks Are a ÷ Se nsory Ap ha sia ( d ifficult to und erstand written and spoken langua ge ) .
* Damage to Broc a Are a ÷ M otor Ap ha sia ( In whic h speech and writing are affec ted but understa nding is inta c t ).

4. Short Te rm M e mory: Involve synaptic changes.
5. Long Te rm Me mory: Involve structural changes & is resistant. ( b ila te ra l hip p oc a mp us le sion ÷ no more ne w long - te rm me m orie s)
----------------------------------------------------------------------

BBB AND C SF :
* BBB consist of endothelial cells of cerebral capillaries and choroids plexus epithelium.
* Lipid soluble subs like CO2, O2, & H2O cross BBB freely but other subs transport (in & out) by carrier in choroid plexus
epithelium.
* Protein and cholesterol are excluded from CSF because of large molecule size.
* Composition of CSF is same as interstitial cerebral fluid of brain.
FUNCTIO N : * BBB maintain constant enviornment of neuron in CNS and prevent scape of CSF and neurotransmitter.
* Non Ionized ( lipid soluble ) drug absorb more easily than ionized ( non lipid soluble ).
* Inflamation, Radiation, or tumor cell may destroy BBB.

C O MPO SITIO N O F C SF & BLO O D C O NC :
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
C SF ~ BLO O D C SF ( BLO O D C SF ) BLO O D
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Na+ K+ M g ++
Cl- C a ++ C re a tinin
HCO3- G luc ose
O smola rity Cholesterol & protein.
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------


TEMP REG ULATIO N :
* Thyroid hormone ÷ | metabolic rate ÷ heat production ( b y stimula ting Na + - K+ ATPa se ) .
* Cold Te mp ÷ Activate sympathetic sys | metabolic rate & heat production ( via | re c e p tors a c tiva tion on b rown fa t)
* Shive ring is most potent heat generating response by Post Hyp otha la mus ( via o & ¸ moto ne uron ÷ c ontra c tions ) .

HEAT LO SS :
* Heat loss response is also control by Post Hyp otha la mus.
* | Temp ÷ + sympathetic tone to the skin and blood vessels ÷ shunting the warm blood near the surface of the
skin ÷ | heat loss by radiation and convection.
* Heat can also loss by evaporation via sweat glands activity which is under sympathetic muscuranic control.

HYPO THALAMUS SET- PO INT FO R BO DY TEMP :
* Te mp se nsors on the skin a nd hypotha la mus re a d the c ore te mp and re la y informa tion to a nt hyp otha la mus which
compare core temp with SET- POINTtemp.
* If core temp is below or above normal it activate SET- POINTheat generating or losing mechanism via Post
hyp otha la mus.
* Cold and Pyogens ( infla mma tory produc ts and media tors ) | the SET- POINTtemp.

KI CK THE BOARDS “USM LE STEP 1” Prepared by Dr. I RFAN M I R M D.
36


FEVER : Pyogens produce IL-1 which act on ant hypothalamus to | the production of prostaglandins which | the SET–
POINTtemp and generate heat (fever).

HEAT EXHAUSTION AND HEAT STO RK :
* He a t e xha ustion: is caused by excessive sweating ÷ + Blood vol ÷ + BP ÷ Syncope .
* He a t stork: occur when body temp | to the point of tissue damage due to impaired sweating response ÷ | core
temp.
* Hyp othe rmia : results when temp is low and shivering & metabolism can not adequately maintain core temp near
SETPOINT.
* M a lig na nt hyp e rthe rmia : caused by inhalation anesthetics in susceptible individual. It is characterized by | in O 2
c onsump tion a nd he a t p rod uc tion b y ske le ta l musc le ÷ rapid | in body temp.
----------------------------------------------------------------------

Fe w Points
* Renshaw cells (neuron) respond to Ach and receptor is nicotinic.
* Parasympathetics contract smooth muscle but relax sphincter by muscarinic receptors.
* Sympathetics relax smooth muscle and contract sphincters by o receptors. exception in eye where o receptors
contract radial muscle and cause mydriasis.
* |1 -- In heart cause contraction where as in kidney cause Renin release.
* |2 -- Relax smooth muscle
* |3 -- In Adipose tissue ÷ lipolysis.

* In carotid sinus Baro receptors respond strong to rising Pressure than falling pressure.
* Protein produce by platelets is thromboplastin.
* Cerebellar lesion cause intention tremor (tremor during voluntary movement). vs.
Parkinson dis cause resting tremor. Imp d iffe re nc e
* Difference b/ w decerebrate and decortical rigidity and other signs ?

KICK THE BOARDS “USMLE STEP 1”

Prepared by Dr. IRFAN MIR MD.

CELL PHISIOLOGY * Cell mem composed of phospholipids bilayer which contain glycerol back bone. * Glycerol back bone composed of head (hydrophilic) and two fatty acid tails (hydrophobic). Tails face each other. * Lipid soluble substance cross cell mem whereas water soluble pass through channel, pores and carriers. * Integral protein span the entire mem (eg. Ion channel) whereas, peripheral protein located either inter or extra cellular side. * Tight Junction (zona occludes) ------- are attachment b/w cells serve intracellular pathway for solute. It may be tight (Impermeable) as in renal distal tubules or leaky (permeable) as in renal proximal tubule or gall bladder. * Gap junction -- is attachment b/w cells which permit IC communication eg. In myocardial cells. * Simple diffusion -- is the transport which is not carrier mediated. It occur down an electrochemical gradient does not require energy  passive. Diffusion can be measured by J = - PA (C1 - C2) (J= flow, P= permeability, A= area, C= concentration) * Carrier mediated transport shows stereospecificity, saturation and competition. Stereospecificty means D-glucose (natural isomer) can transported where as L-glucose (L-isomer) can not. Saturation means transport  as the concentration  until carriers are saturated called Tm (transport maximum) Competition means structurally related solute compete for transport site. eg. (Galactose is competitive inhibitor of glucose in small Intestine). * Facilitated diffusion -- occur down an electrochemical gradient, does not require energy  is passive. It is carrier Mediated and more rapid than simple diffusion. * Primary Active transport -- occur against the electrochemical gradient (up hill). It utilize metabolic energy (from terminal bond of ATP)  is active. It is also carrier mediated ( exhibit stereospecificity, saturation and competition) . Eg. Na+ - K+ ATPase (usual stoichiometry is 3Na / 2K) ,Ca++ ATPase in sarcoplasmic reticulum, K+ - H+ ATPase in parietal cells. * Secondary Active transport -- in which transport of two or more solute is coupled. One of the solute is transported down hill (usually Na+) which provide energy for uphill transport of other solute. Metabolic energy provided indirectly from Na gradient. Thus the inhibition of Na+ - K+ ATPase results into inhibition of Secondary transport. Eg. Na+ - glucose Cotransport in renal proximal tubule, Ca++ - Na+ exchange, Na+ - H+ exchange. Poisoning the Na+ - K+ pump eventually results into inhibition of Ca++ - Na+ exchange due Na+ imbalance across cell mem. * Cotransport or symport is transport of solute in the same direction whereas, Counter transport or antiport or exchange is the transport of two solute in opposite direction to each other. * Osmolarity is the conc (C) of osmotically active particle in a solution. Osmolarity = g  C (g is no of particle in the solu. * Solution with high osmolarity is hyperosmotic, low osmolarity is hypoosmotic, and same osmolarity is isosmotic. * Osmotic Pressure (van’t Hoff’s Law) depends on the conc of osmotic particles.  in solute particle results in  osmotic P. It can be measured by  = g  RT  C (Where R is gas constant 0.082L - atom/mol - K. and T is absolute temp K). * Reflection coefficient is the no b/w zero & one. It explains the ease with which solutes permeate the mem. If Reflection coefficient is 1 the solute is impermeable & when it is zero solute is permeable. eg. Reflection coefficient of albumin (big solute) is 1 where as urea (small solute) is zero. * Ion channels are open or closed by gates. It may be voltage gated channel which open or closed by change in mem potential. Eg Na channel in nerve action potential. It may be Ligand (chemical) gated channel which open or closed by hormones, second messenger, neurotransmitters. * Diffusion potential is the potential difference generated across a mem because of conc difference of an ion. * Equilibrium potential is the diffusion potential which exactly balance (opposes) the tendency for diffusion caused by conc difference. There is no more net movement because electrical driving forces on ion are equal and opposite.. * Nernst equation is used to calculate equilibrium potentials. E = -2.3 RT log10 [Ci] zF [Ce] E Na+ is + 65mV E Ca++ is + 120Mv E K+ is - 85mV E Cl- is - 90mV * Resting mem Potential is the measured potential difference in mV (millivolts), it is established by diffusion potential. The resting mem potential of nerve is -70 mV. At rest nerve mem is far more permeable to K+ than to Na+ at rest. * Threshold is the mem potential at which occurrence of action potential is inevitable. Inward current depolarize the mem to Threshold.

1

KICK THE BOARDS “USMLE STEP 1”

Prepared by Dr. IRFAN MIR MD.

* Upstroke of action potential is depolarization cause rapid opening of the activation gates of Na+ channel. Na enters into the cell. * Depolarization also open K+ gates and closes the Na+ channel gates but at slower rate. This combined effect make K+ conductance higher than Na+ conductance in last quarter of depolarization which make mem potential to Repolarize. * Repolarization is caused by outward K+ current. * Over shoot is the portion of action potential when mem potential is positive whereas Under shoot (hyperpolarization) makes the mem potential more negative (close to K+ equilibrium potential). * Absolutely Refractory period is the period during which another action potential cannot be elicited no matter how large the stimulus is. * Relative refractory period begins at the end of absolute refractory period and continuous till mem potential return to its resting potential. Stronger than usual current can elicit the action potential. *  Fiber size and myelination can  the conduction velocity of action potential. Remember myelinated nerve exhibit saltatory conduction because action potential can be generated only at the Node of Ranvier. * End Plate potential (EPP) in the postsynaptic mem is not an action potential but a depolarization of specialized muscle end plate. Once the end plate region is depolarized local current cause depolarization and action potential in the adjacent muscle. * Excitatory postsynaptical potential (EPSP) bring the cell closer to fire action potential where as Inhibitory Postsynaptical potential (IPSP) hyperpolarize the postsynaptical cell by opening Cl- channels.. * Thick filament contain myosin present at A band. vs. Thin filament contain actin, tropomyosin & troponin present at  band. * Myosin head bind ATP and actin and are involved in cross bridging formation. * T tubule are present at the junction of A band and  band. It carry depolarization to the interior of the cell. * Skeletal muscle contraction -- sarcoplasmic reticulum (SR) are internal tubular structure site of Ca++ storage and release. Ca bound loosely to calsequestrin with in SR & it release upon depolarization bring by T tubules. Released Ca+ bind to troponin C on the thin filament causing conformational change in Troponin (which is tropomyosin moving out of way so that cross bridge cycle can begin). Actin myosin binds and filament slide over each other and ATP is hydrolysed. * Length Tension relationship :1. Passive tension -- is tension developed by stretching to Fixed length (preload). 2. Total Tension -- is tension developed when the muscle is stimulated to contract at different length. 3. Active Tension -- is the difference b/w total tension and passive tension. * Smooth muscle contraction -- smooth muscle has thick & thin filament & are not arranged in sarcomere. (vs. striated m) There is no troponin instead Ca++ regulate myosin on thick filament Ca++ enter in the cell across cell mem it may cause release of additional Ca++ from SR via Ca++ - gated channels. Hormones and neurotransmitters also release Ca++ from SR through IP3 gated Ca++ channels. IC Ca++ . Ca++ bind to Calmodulin and Ca++ - calmodulin complex bind to and activate myosin light chain kinase which further phosphorylate myosin and allow it bind with actin. Contraction follow. * Dephosphorylation of myosin cause relaxation where as in striated muscle Ca++ uptake cause relaxation. Remember in heart and striated muscle Ca binds with troponin and in smooth muscle Ca binds with calmodulin. Figs:

2

ENODCRONOLOGY ** SECOND MESSENGER SYSTEM :--------------------------------------------------------------------------------------------------------------------------------------CYCLIC AMP CRH ACTH TSH PTH ADH ( V2 ) 1. LH. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------* Causes of  or  secretion of ADH ::  Secretion of ADH vs. T4 TYROSINE KINASE Insulin IGF CYCLIC GMP ANF EDRF (NO) --------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------* TSH.  Endorphin.*  Glucose uptake ( Diabetogenic ) *  lipolysis *  Protein Synthesis (  LBM ) *  Production of IGF (insulin like growth factor) * Somatostatins and Somatomedins have imp negative feed back function. PL secretion  by TRH and inhibit by Dopamine. all derived from POMC. vs. HCG are the member of same glycoprotein  bears  subunit (identical) &  subunit (unique for hormone). * ACTH. Function:-* Lactogenesis * Breast development * Inhibit Ovulation ( via  Syn of GnRH ) * inhibit spermatogenesis (via  GnRH) Pathology :. * Neurophysin is CNS carrier protein for both hormone (ADH.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. MSH. Functions :. IRFAN MIR MD. *  MSH. Oxitocin). Somatomedins cause +ve feedback on the release somatostatin from HT -------------------------------------------------------------------------------------------* PL (acidophilic to chromophobic stain). 2 FSH. sight and sound of infant. Nausea (strong) *  Agonist * Hypoglycemia * ANP * Necotinic opiate * Antineoplastic drug ----------------------------------------------------------------------------------------------------------------------------------------------------------------------- 3 . Act on receptors V1 ( vasoconstriction ) and V2 (  distal tubule and collecting duct permeability) * Oxitocin originate in paraventricular nuclei of hypothalamus ( post lobe ).  secretion of ADH ----------------------------------------------------------------------------------------------------------------------------------------------------------------------*  serum osmolarity *  serum osmolarity * Vol contraction * Ethanol * Pain.  Lipotrophin. M3 GABA STEROIDS Mineralcorticoids Glucocorticoids Estrogen Progesterone Testosterone Vit D T3. * GHRH  GH (acidophillic stain). FSH. and  MSH Rudimentary in adult. 2. Major stimulus for secretion is Suckling.* Failure to lactate * Failure to ovulate * Galactorrhea (hypothyroidism can cause increase in TRH with resultant galactorrhea) -------------------------------------------------------------------------------------------* ADH originate in supraoptic nuclei of hypothalamus ( Post lobe ). * Somatostatin block GHRH effect on AP. LH HCG M2 MSH Calcitonin Glucagon Secretin Dopamine IP3 Ca++ GnRH TRH GHRH ADH ( V1 ) Oxitocin 1 Angiotensin II CCK M1 .

* Hypoparathyroidism  Tetany (  Ca++. its deficiency results into  T3 and Reverse T3.) present in thyroid follicular epithelial cell.I 2 + Tyrosine of Thymoglobulin  MIT + DIT 3. 3.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. (Basophilic and chromophobic stain) * Iodide pump ( I . Hashimoto thyroiditis. Growth.1.  Ph ). Contraction of uterus.  PTH Action on Bone :Action on Kidney : Resorption  Ca++ Reabsorption  Ph Reabsorption  Ca++ Absorption (via Vit D)  Resorption  Ca++ Reabsorption  Ph Reabsorption  Ca++ Absorption (via vit D Ca++ binding Protein) *  Reabsorption Action on Intestine :Overall effect :- Serum Ca++  Serum Ca++  * Serum Ca++  Serum Ph  Serum Ph  ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- * Resorption of organic matrix of the bone is reflects in  Hydroxyproline Excretion. * Enz 1. Irritation. Palpitation etc. Hypothyroidism ( Myxedema. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------PTH VIT D CALCITONIN ------------------------------------------------------------------------------------------------------------------------------------------------------------------------Stimulus for secretion: Serum Ca++  Serum Ca++ *  Serum Ca++ Mild  in serum Mg  Serum Phosphat Severe  serum Mg inhibit secretion. * T3. CNS -. * T3 is 4 times more potent than T4.MIT + DIT  Triidothyroxine T3 ( active form ) DIT + DIT  Thyroxine T4 * Befor release Iodinated thyroglobulin first must be taken back into the follicular cell from lumen for digestion of thymoglobulin by lysosomal enz to release T3 T4. T4 syn can be inhibited by  dosis of Iodine ( I 2 ) this is called Wolf Charkoff Effect. and maturation. * TRH  TSH  T3.5 monodeiodinase cause break down of T3 and Reverse T3. 4.cells ) of thyroid. IRFAN MIR MD. * Iodide pump Inhibit by Thiocyanate and Perchlorate ion. 2. Its major action is to inhibit bone Resorption. 4 . Metabolic effect are over all catabolic . BMR :.2 I .Prenatal CNS maturation In Adults ---. etc. * Grave dis in which IgG ( thyroid stimulating imunoglobin)   T3. * Calcitonin Syn and secreted by Parafollicular cell ( C. Milk ejection. * Three stages of TH syn :. De Quervian thyroiditis. 2. Adrenergic Stimulation. listlessness. Bone formation. Gonad and Brain (results into  body temp). ( left over MIT and DIT are digested by thyroid deiodinase ). slow speech.  Syn of Na+ K+ ATPase (results into  O2 consumption)  HR. Reidal thyroiditis )   mental capacity. ( it can be used to induce labour ). Autonomic nervous sys :. O2 consumption and BMR except in Spleen. * T3 T4 circulate by Thyroid Binding Globulin. Plummers $ )  Hyperexcitability. impaired memory.25 Dihydrocholecalciferol is active form of Vitamin D. * 1.( Propylthiouracil inhibit oxidation). Somnolence. Organification :. T4 ( stored in lumen).( Iodide )  I2 ( iodine ) --------. Cretinism. Oxidation :. * Conversion of T4 into T3 (active form) and Reverse T3 (inactive form) take place in target tissue by enz Iodinase. * PTH  Vit D production ( indirectly ) by stimulating 1  Hydroxylase. * Function of thyroid hormone :1. * Function of Oxitocin : Myoepithelial contraction of mammary gland.  Ventilation (ensure more O2 delivery to tissue) 5. produce by 1 hydoxylase in kidney to Provide Ca++ & Phosphate for normal bone mineralization. * Vit D mineralize new bone by  Ca++ and Ph in serum.Hyperthyroidism ( Grave’s dis. Coupling reaction :. Dilatation of Cervix and Orgasm. T4 -------------------------------------------------------------------------------------------------------------------------- * PTH is secreted by Chief cells and regulate serum Ca++. * PTH  Ca++ reabsorption at distal tubule where as in proximal tubule PTH  inhibit Ph reabsorption with resultant excretion of nephrogenous cyclic AMP.

25 (OH)2 Cholecalciferol * Remember  PTH.  Def of 11  hydroxylase  Absence of Cortisol only ( because 11.25 hydrocholecalciferol 24. * Vit D Deficiency  Osteomalacia and Rickets .  Bone resorption ( with resultant  in calcitonin & Vit D). Ca++.1.  lipolysis  glucose utilization (hyperglycemic) 2. * Hyperparathyroidism  Ca++. and  Ph have positive stimulating effect on enzyme 1 Hydroxylase hence ↑ it activity.CRH (from paraventricular nuclei)  ACTH (AP) .  3  hydroxysteroid dehydrogenase  3  hydroxysteroid dehydrogenase Hydroxyprogesterone  Androstenidione 17.  Deficiency of 17. Cortisol cause -ve feed back inhibition to both CRH and ACTH. Cortisol  at 6 AM and  at 12 midnight. * Hyperkalemia cause  Aldosterone secretion. * Pseudohypoparathyroidism ( Albright hereditary Osteodystrophy ) is due to defective G Protein in target tissue with resultant resistance to PTH which cause  PTH. 3. Ph ) 1.  Deficiency of 3  hydroxysteroid dehydrogenase  Absence of every thing. * ACTH up regulate its own receptor. Release in circardian rhythm.Glucocorticoids (Corticosteroids) Zona R -.deoxycorticosterone has partial Aldosterone activity 3% ) 5 .  H+ secretion.Androstenidione produce Testosterone in testes and Estraidol in ovary. Estradiol) ** Cholesterol  Pregnenolone 17  Hydroxylase  17 . serum Ph. 20 lyase  Absence of Androgen.  cortisol level cause bone resorption. phosphaturia.  Deficiency of 21  hydroxylase  Absence of Glucocorticoids and Mineralcorticoids. Anti inflammatory :. 20 Lyase  17 Hydroxypregnenolone Dehydroxyandrosterone  3  hydroxysteroid Dehydrogenase Progesterone   21  hydroxylase 11 Deoxycorticosterone 11 Hydroxylase corticosterone AT II & ↑K+    Aldosterone synthase Aldosterone .  Ca++.  K+ secretion. 20 lyase 17 Osteroid dehydrogenase 21  hydroxylase   and Aomatase 11 Deoxycortisol Testosterone / Estradiol  11 Hydroxylase Cortisol * Glucocorticoids :. ------------------------------------------------------------------------------------------------------* Zona G -. Gluconeogenesis :.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. IRFAN MIR MD. Cholecalciferol ( In Liver )  Kidney   ( 1  Hydroxylase )   ( PTH.OH. * Glucocorticoids are essential in response to stress. Urinary cAMP. (Both synthesize by POMC). * Glucocorticoid Functions :. Maintain vascular responsiveness to catecholamine.Androgen (Testosterone. Diet  cholecalceferol  7 Dehydrocholecalciferol ( In skin through ultra voilet light )  25. * Mineralcorticoids :* Hypovolemia   Renin  AT I  AT II   Aldosterone   Na+ reabsorption. * Androgens :.cell proliferation ) inhibit histamine and serotonin.syn of lipocortin inhibit phospholipase A2 inhibit IL2 ( so inhibit T.  Ca++.Mineralcorticoids (Aldosterone) Zona F -.  Ph. protein catabolism and  protein syn.

1. Glucagon   Fructose 2. striae. and Ketone production). ( That's why also cause gluconeogenesis. Ach ------------------------------. uptake of glucose and promote glycogen formation.Somatostatin. Adrenocortical Excess .( hypertension. Gastrin.  cortical & androgen level.  ACTH. metabolic acidosis because aldosterone is normal. somatostatin and EN. AA. Hyperaldosteronism (Conn $) -. cells ---. supraclavicular fat. * Pathology :. * Somatostatin :.  suppress gonads function in both sexes. hyperkalemia.  Virilization of female (early linear growth.Glucagon  cells ---. Water house Friderichson $ :. Decreases Fatty acid .   ACTH  hyperplasia of Zona F and Zona R . hypotension and nocturia. central obesity.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. 3. Lipolysis.   Adrenal androgen.  Pancreatic polypeptide :------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Insulin ( Tyrosinekinase receptor) stimulation for secretion Over all Effect -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- blood glucose  blood glucose  AA  Fatty acid Glucagon GIP --------------------------------------------- AA GH --------------------------------------------- Fatty acid hypokalemic  Cortisol --------------------------------------- Ketoacid ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Glucagons ( cAMP mech ) Stimulation for secretion Over all Effect --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Blood glucose  Blood glucose  AA CCK --------------------------------------------- Fatty acid EN.  Does not exhibit vol contraction. Action :. and serum K+ concentration Inhibit lipolysis and stimulate fat deposition.  renin secretion ) 4.cause by tumor. moon face buffalo hump. pubic and axillary hair).  Cortisol and Aldosterone. osteoprosis.21  hydroxylase deficiency -.  Blood glucose. 2.Intermix ---.Outer cell islet ---.   Hydroxyprogesterone and progesterone.  Cushing Dis  Overproduction of ACTH. hyperkalemia. 5. ketones. 6 . Nor EN. muscle wasting. in addition to Glycogenolysis. Receptor  in starvation and  in obesity. * insulin secretion is mediated by ca++ channel opening in  cell.Central islet ---. hypertension.6 Biphosphate production and  Phosphofructokinase activity.Catastrophic adrenal insufficiency due to hemorrhagic necrosis of adrenal cortex often because of Meningococcal meningitis . Adrenogenital $ :. metabolic acidosis Aldosterone def. vol contraction. * Insulin consist of  subunit and  subunit among which  subunit have tyrosine kinase activity. Adrenocortical Insufficiency (Adison dis) . hyperglycemia. * Insulin def → into hypokalemia. and Intestinal absorption of Glucose. Secondary  Caused by  ACTH . hypokalemia.Inhibit secretion of Glucagon. Insulin. mineralcorticoids and androgen   POMC. Inhibit Glycogenolysis and  Gluconeogenesis. * Insulin down regulates its own receptor. Primary  Commonly cause by autoimmune destruction of Adrenal cortex. metabolic alkalosis.  Cushing $  commonly cause by Glucocorticoid therapy and adrenal gland hyperplasia.  Hypoglycemia. Ketoacid (  Hydroxubutyrate and acetoacetate ) ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- * Glucagon act only on liver  Glycogen break down.   glucocorticoids. Gastrin.Insulin  cells ---. poor wound healing. Also ketosis which results into metabolic acidosis  compensatory hyperventilation. virilization of female. Nor EN  insulin secretion. IRFAN MIR MD. -------------------------------------------------------------------------------* Endocrine Pancrease :. hyperpigmentation.

Ovulation Leutinization  LH  FSH  Theca cell Granulosa cell   aromatase Testosterone ( Androgen ) Estrogen (convert Androgen into estrogen) LH  FSH  Cholesterol  Pregnenolone  17 Hydropregnenolone  dehydroepiandrosterone  androstenidione  testosterone (theca cell) ↓ Aromatase 17 estradiol.ve and + ve feed back effect on FSH and LH secretion. IRFAN MIR MD. Cholesterol desmolase Cholesterol  Pregnenolone   LH 17 hydroxypregnenolone  Dehydroxyandrosterone  Androstenidione 17  OH steroid Dehydrogenase  Testosterone 5  reductase  Dihydrotestosterone (active form) ( Inhibin release from sertoli cells. *  Size and secretory activity of epididymus. Development of breast. 6. * Estrogen Function :1. * In male LH hormone cause testosterone synthesis in leydig cells where as in female it cause testosterone synthesis in theca cells. . Follicular development beyond the antral stage. Development of female sec sexual characterstics. GnRH upregulate its own receptor in AP.* Prenatal differentiation of wolfian duct and external genitalia. 3. Maintainance and Maturation of fallopian tube. cervix. 4. 8. uterus. * Maintain spermatogenesis (by paracrine effect of testosterone) and increases libido. (granulosa cells) * Aromatase convert testosterone into 17 Estradiol. and vagina. LH. ----------------------------------------------------------------------------------------* ESTROGEN AND PROGESTERONE :HT  GnRH  AP * FSH and LH  Cause Steroidogenesis in ovarian follicle & corpus luteum. Stimulate PL secretion but block its action on breast. Vasdefrens. Prepared by Dr.KICK THE BOARDS “USMLE STEP 1” * Testosterone synthesize by 5  reductase and secreted by Leydig cells. ( where as progesterone cause . Development and proliferation of granulose cell. 7 . 5. * Cause pubertal growth spurt. Maintain pregnancy. Upregulate estrogen. * In male FSH cause spermatogenesis in sertoli cell where as in female it cause 17 Estradiol synthesis in granulose cell. * Develop male Secondary sexual characteristics at puberty. prostate and seminal vesicle. it cause .(progesterone Raise uterine threshold to contractile stimuli during pregnancy) 9.ve feed back ) 2. Testosterone Action :. Lower uterine threshold to contractile stimuli during pregnancy vs. and progesterone Receptor. 7.ve feed back affect on the release of FSH from Ant pituitary ) * GnRH originate from arcuate nuclei of hypothalamus & secrete in pulsatile manner. * 5  reductase inhibit by Finastride it can be used in BPH.

4):. 4.In which Primodial follicular development and uterus proliferate. LH. Leuteal Phase (day15 . .Occur 15 days prior to menses regardless of cycle length. LH suppressed And Progesterone is low.28) :. Ovulation (day 15) :. Estrogen  just after ovulation and  again in leuteal phase (source of this  is corpus leuteum) Cervical mucous  and become less viscous.ve AP Progesterone . 4.ve feed back effect on FSH. If fertilization occur Estradiol and progesterone keep  steadily.Is sloughing of endometrium because of with drawal of Estradiol and progesterone.Corpus leuteum develop and syn of estrogen and progesterone occur from it. Responsible of development of breast. 3. LH (responsible for LH surge). ------------------------------------------------------------------------------------------------------------------------------------------------------------------------Phase of Cycle Hormone Type of Feed Back Site ------------------------------------------------------------------------------------------------------------------------------------------------------------------------Follicular Phase Estrogen . Raise uterine threshold to contractile stimuli during pregnancy vs. 3. Basal body temp  (progesterone act on HT thermoregulatory center) If fertilization not occur corpus leuteum regresses   Estradiol and Progesterone. ---------------------------------------------------------------------------------------- 8 . Menses (day 1 . IRFAN MIR MD. Estradiol  steadily and FSH.ve HT ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Fig: * Menstrual cycle :1.  + ve & . Maintain secretory activity of uterus in luteal phase.ve and + ve feed back ) 2. Maintain pregnancy.KICK THE BOARDS “USMLE STEP 1” * Progesterone Function :1. Estrogen Lower uterine threshold to contractile stimuli during pregnancy. 5. Follicular phase (day 5 . 2.ve AP Mid Cycle Estrogen + ve AP (ovulation occur) Luteal Phase Estrogen .ve FEED BACK CONTROL OF MENSTRUAL CYCLE. ( where as estrogen cause both . Ovulation occur as a result of estrogen induced LH surge. Prepared by Dr.  vascularity and secretory activity of endometrium.. Estradiol  + ve feed back on FSH.14) :.

Submucosal plexus and Myenteric plexus -. Circular muscle --.HCG stimulates corpus leuteum to produce Estradiol and progesterone. PL also antagonise the action of FSH and LH on ovaries. Major Placental Estrogen is Estriol. Extrinsic nervous sys:. rectum and anus ) 9 . pancreas & upper large intestine where as pelvic supplies to lower large intestine. IRFAN MIR MD.contraction cause decrease in diameter of the lumen. --------------------------------------------------------------------------------------------GI PHYSIOLOGY * STRUCTURE AND INNERVATION : Epithelial cell may be secretive or absorptive.PL  steadily during pregnancy but estrogen and progesterone block the action of PL on breast.consist of extrinsic nervous sys and intrinsic nervous sys. *2nd & 3rd TRIMESTER : Progesterone produce by placenta & estrogen produce by fetal adrenal gland & placental Interplay. Ovulation is suppressed by PL because PL inhibit GnRH secretion from HT with resultant  in FSH and LH. Longitudinal muscle --.contraction cause change in surface area. Muscularis mucosa --. ( Vagus supplies to esophagus . HPL (Human Placental Lactogen). HCG peak occur at week 9 and than it declines.contraction cause shortening of GI segment. Fig: * INNERVATION OF GI TRACT :.Initiating event is unknown. stomach.L2.is enteric nervous sys which integrate and coordinate the motility. *1ST TRIMESTER :. Parasym is Excitatory via vagus & pelvic nerves where as sym is inhibiting originate from T8 . (there is no change of blood oxitocin level prior to labor even though it is potent stimulator of uterine contraction) * LACTATION :.Comprise of Sympathetic and Parasympathetic nervous sys.KICK THE BOARDS “USMLE STEP 1” * PREGNANCY :- Prepared by Dr. Suckling stimulates both oxitocin and PL secretion. secretion and Endocrine function of GI tract. After parturition estrogen and progesterone  and lactation occur.has GH and PL like effect produce through out pregnancy * PARTURITION :.

pyloric. mucosa of intestine & colon) Distention of stomach . fatty acid. Inhibit H+ secretion. stimulate pancreatic HCO3 secretion & inhibit Gastric H+ secretion. Secretin.(atropin does not inhibit Gastrin release because mediator of gastrin release is GRP not Ach) Inhibit by H+ in stomach via Somatostatin. Post ganglion adrenergic fiber synapse in submucosal and myenteric plexus. Preganglionic cholinergic fiber synapse in prevertebral ganglion. Phenylalanine and Tryptophan stimulate growth of gastric mucosa. Intrinsic sys also relay information with in GI by local reflexes. (prietal cell. Neurocrine (only 3) ------. Gastrin releasing peptide (Bombesin). Some direct post ganglionic adrenergic innervation to blood vessel & smooth muscle also occur here. Inhibit gastrin on growth of gastric mucosa. Stimulate biliary HCO3 secretion. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- * GI paracrine: Somatostatin -. Somatostatin inhibits all GI hormone and gastric H+ secretion Histamine ------. * GI neurocrines: VIP Cause GI smooth muscle relaxation. Intrinsic nervous sys:. Enkephlins also inhibit intestinal secretion of fluid and electrolytes. Enkephlins -. * GI HORMONES :Hormones (only 4) ---------. CCK (33AA) Gastrin I cell of doudenum & Jejunum Small peptide and AA. & its secretion is inhibited by vagus nerve.Secrete by mast cell induce gastric H+ secretion Histamine also potentiate its effect on Ach and gastrin   H+ secretion. Secretin Glucagon S cell doudenum H+ and fatty acid in Doudenum (Gastric Inhibitory peptide) GIP Secretin Doudenum and Fatty acid. leu E) Neurocrine synthesize in neuronal body move down by axons & release by nerve action potential. CCK.Little gastrin have 17 AA.Gastrin . Glucagon jejunum Glucose.Intrinsic sys relay information to and from GI to CNS. Myenteric plexus (Auerbach.Contract GI smooth muscle of lower esophageal. Stimulate pancreatic HCO3 and H2O secretion. 10 .Secreted in response to H+ through out GIT. Inhibit H+ secretion.It enter portal and sys circulation and act on distal sites. * Gastrin ---. AA specially  gastric H+ secretion. IRFAN MIR MD. Secrete pancreatic HCO3 via secretin. & Orally administered Stimulate insulin release. monoglycerides. Gastrin’s 4 C terminal AA contain biologic activity. (but not triglycerides) Contraction of gallbladder & relax sphincter of oddi. are potent stimulater. Growth of endocrine pancrease & gall bladder mucosa.s plexus) control motility of smooth muscle Submucosal plexus (Meissner.release from nerve ending by vagal stimulation  stimulate Gastrin release. ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Hormones Homology Site of secretion Stimulus for secretion Action ------------------------------------------------------------------------------------------------------------------------------------------------------------------------Gastrin CCK G Cell (stomach) Small peptide. Gastrin is a potent H+ releaser than histamine. Big gastrin have 34 AA (it is not a dimer of little gastrin).VIP(vosotive intestinal peptide).s plexus) receive sensory information from chemo and mechano receptor and control secretion and blood flow.  growth of exocrine pancrease. Enkephalin (met E. Inhibit gastric emptying. Paracrine (only 2) ----------. Secrete pancreatic enz. VIP producing pancreatic tumor of islet cell  pancreatic cholera GRP (bombesin) -. and iliocecal sphincter. AA. * Secretin --.Somatostatin and Histamine --.Release from GI cells and act on short distance. Vagus via GRP. GIP --.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr.all AA require for biologic activity. CCK also has gastrin like activity .

* Frequency of slow wave lowest in stomach (3/min) and highest in doudenum (12/min). IRFAN MIR MD. * Peristaltic contraction  coordinated by enteric nervous system & propel food downward.occur when tone of esophageal sphincter  or secondary peristalsis does not clear food particles. * Valsalva maneuver :. mixing occur and food propel to doudenum. * Parasympathetic activity cause rapid gastrocolic reflex whereas CCK & Gastrin slows down the gastrocolic reflex.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. * Orad region ---.when lower esophageal sphincter does not relax. * Primary peristalsis create just behind the food and secondary peristalsis clear the esophagus. * Haustra is a sac like segment appear following segmental contraction of colon (during mixing the colon content). upper esophageal sphincter relax (gravity accelerate the movement).contain Oxyntic gland vasovagal reflex relax Orad region. * Frequency of slow wave not influence by neuronal or hormonal input where as action potential yes. * SWALLOWING REFLEX coordinated in medulla. perstalsis begin. * Once rectum is filled about 25% cause urge to defication (it can be prevent by voluntarily by external sphincter). * Lower esophageal sphincter relax (via vagus nerve neurotransmitter is VIP) at the same time Orad stomach relax (receptive relaxation) CCK participate in it by increasing dispensability of Orad stomach.There are 3 major glands. * At rest intraesophegeal P is < than atmospheric P.contraction.( contraction behind bolus and relaxation in front of bolus ) * Gastroileal reflex  deliver intestinal content in colon. maxillary and sublingual gland. * Depolarization of slow wave bring mem potential closer to threshold to initiate action potential. upper 1/3 of esophagus and external anal sphincter which are straited muscle. * Slow wave are oscillating mem potential which is essential to smooth muscle. At highest flow rate saliva has osmolarity close to plasma. Motilin cause those contraction.voluntary increasing of intraabdominal P by expiring against closed glottis. iliocecal and internal anal sphincter. Tonic contraction ------. Phasic Contraction ---. Parotid.( Aldosterone act on ductal cell   reabsorption of Na+ and secret K+ ) * Duct is relatively impermeable to water  hypotonic saliva * Parasympathetic stimulation is through facial nerve VII and glossopharyngeal nerve IX   production of saliva (receptors are muscarinic and 2nd messenger is IP3 where as sympathetic stimulation also cause  production of saliva but receptors are  and 2nd messenger is cAMP. * MIGRATING MYOELECTRIC COMPLEX :* Are contraction that occur at 90 min interval during fasting which clear stomach. * H+ in doudenum inhibit gastric emptying by direct neuronal reflex via GI plexus. vs. (Oxyntic gland secrete Hcl and Intrinsic factor) * Caudad region ---. in turn food accumulates in esophagus. antrum and intestine. * Slow wave are not action potential but they do determine the pattern of action potential and contraction. * Gastric emptying is fast when contents are isotonic and is slow when contents are hypertonic or fatty. Reflex mediated by ANS and gastrin. * Segmental contraction  mixing of contents in orad and caudad direction but no net movement of food occur .and secreting K+ and HCO3. * The Acinus produce initial saliva whose composition is same as plasma but duct modify the saliva by reabsorbing Na+ and cl. * Gastrocolic reflex : Is food in stomach which  the motility of the colon and frequency of mass movement.found in lower esophagus sphincter. * Food in stomach   gastro colic reflex   frequency of mass movement.contraction and relaxation found periodically in esophagus.(myoepithelial and ductal cells contract to eject saliva in mouth) * At lowest flow rate saliva has lowest osmolarity &  K+ conc vs. larynx elevate (glottis close). * SALIVA :. vagus & glossopharyngeal nerve carry info to & from the medulla. * Gastric reflux ---. Intrathoracic P can be measured by baloon catheter. 11 .Contractile tissue of GIT is unitary smooth muscle except pharynx. orad stomach. * GI MOTILITY :. * During swallowing beathing inhibit. nasopharynx close. * Achalasia ---.

* Chyme in the doudenum inhibit H+ secretion directly or via hormone GIP (release by fatty acid in stomach) & Secretin (release by H+ in duodenum). * In vomiting H+ is lost and results into Metabolic Alkalosis (arterial Blood become Alkaline) --------------------------------------------------------------------------------- 12 . Cemetidine. Ach (vagal) Ach (vagal stimulation) see above Ach (vagal stimulation) --------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- * Gastric Secretions --. which further inhibit H+ secretion via somatostatin. * When stomach is empty its PH is < 3.  K+ Hypotonic  amylase (starch) Lingual lipase (triglycerides) Kellikrein HCl STIMULATED BY IP3 parasympathetic (imp) cAMP sympathetic (  ) Prepared by Dr. Gastrin is high  and Gastric perital cells are  because of gastrin mediated growth.KICK THE BOARDS “USMLE STEP 1” GI SECRETION Saliva CONTENTS  HCO3 . Fig: * Chief cells secret Pepsinogen in the form of zymogen granules. Histamine (H2) via cAMP parasympathetic  PH of stomach Chyme in doudenum Atropine. Histamine. INHIBITED BY Sleep Dehydration Atropine (anticholinergic) ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Gastric Gastrin. pepsinogen STIMULUS FOR SECRETION Gastrin.0  inhibition of gastrin release.Gastrin secreting tumor of pancreas   H+ secretion & is not subject to . omeprazole Pepsinogen Intrinsic factor -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------CELL TYPE Oxyntic (parietal cell) Chief cell (peptic cell) G cell Mucous cells SITE Fundus Fundus (Body) Antrum Antrum PRODUCT HCl Intrinsic factor Pepsinogen (convert to pepsin at low PH) Gastrin mucous.ve feedback inhibition of H+. * In gastric ulcer H+ is lower than normal and Gastrin is  * In duodenal ulcer H+ is higher than normal. * Zollinger Ellison $ --. Ach. IRFAN MIR MD.HCl is secreted by parietal cell into lumen of stomach and HCO3 absorbed in blood stream and HCO3 absorbed in venous blood (Alkaline Tide) later it secreted back into the lumen of the GI tract via pancreatic secretion to neutralize H+ in small intestine. vagotomy.

maltriose. ----------------------------------------------------------------------------------------------------BILE SECRETION AND GALL BLADDER:* Bile contain bile salts. * In water bile salt orient them selves around droplet of lipid and keep the lipid disperse in solution (emulsified). amylase. galactose absorption stops. * Bile salt are Amphiphatic having hydrophobic and hydrophilic portion. *  Amylase (salivary and pancreatic) hydrolyze 1. Trehalase also yield monosaccharide form disaccharides. Due to ilieal resection or diseased ileum. * Glucose. IRFAN MIR MD. &  limit dextrin which is further hydrolyze to yield glucose. * Intestinal bacteria convert primary bile acid to secondary bile acid (deoxycholic acid and lithodeoxycholic acid). * Regulation of Pancreatic secretion :. galactose. fructose). pointing there hydrophilic portion into the aqueous solution to make it soluble for absorption. * Lactase. * Fructose absorption in the intestinal cell occur by facilitated diffusion ( so can not absorb against its  gradient). where as Na . * Bile is produce by hepatocytes continuously (chloretic agent increase bile formation). 13 . phospholipids.K pump at basolateral side maintain IC Na+. * Bile depletion cause statorrhea. vs. ---------------------------------------------------------------------------------------------------DIGESTION AND ABSORPTION : CARBOHYDRATE -. It contain lipase. * Terminal ileum absorbes conjugated bile acid with Na+ by sec active transport. * Na+. * Lactose intolerance occur when brush border lactase is  or absent  lactose cant be absorb  H2O remains in lumen  results in osmotic diarrhea. small peptide.Absorbs only in the form of monosaccharide (glucose. fatty acid in duodenum. for e.conc is lower than plasma. galactose & fructose by enz maltase.(HCO3 . * PANCREATIC SECRETION :* Pancreatic juice is high in vol having same Na+. * Secretin acts on pancreatic ductal cell   HCO3 secretion (via cAMP) where as CCK acts on Pancreatic Acinar cell   enz secretion (via IP3).is low. * primary bile acid (cholic acid and chenodeoxycholic acid) is syn in hepatocytes than conjugate it to glycine and Taurine to form the respective bilesalt.4 glycosidic bond in starch & yield oligosaccharides maltose. K+ conc as plasma where as HCO3 conc is higher than plasma.It is regulated by secretin and CCK. saliva ) * At low flow rate HCO3 is low and Cl. * Cystic Fibrosis --. Ach cause only contraction of Gall bladder.Defect in Cl channel because of mutation in the Cystic fibrosis Transmembrane conductance (CFTR) gene Which results into deficiency of pancreatic enz  mal absorption (statorrhea). bile pool depletion and Anemia.is high where as At high flow rate HCO3 is higher and Cl.  dextranase & sucrase (brush border enz). Galactose entered the intestinal cell by Na+ dependant Sec active transport (Cotransport) later it entered blood by facilitated diffusion. * Ach (via vagal reflex) stimulate enz secretion by Acinar cell in response to H+. * Glucose and galactose absorbs with Na+ as a sec active transport. * Bile salt form Micelles by covrering one fatty acid and two monoglycerides. K+ conc is not effected by flow rate ( vs. If this pump is poisoned Glucose. CONTRACTION OF GALL BLADDER :* CCK cause contraction of gall bladder & relax sphincter of Oddi. and Cl.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. * The Acinar cell produce initial pancreatic juice Na+ and Cl-. AA. protease. cholesterol.g. * Aqueous component is varies with flow rate. * Pancreatic juice has isotonicity.Cl exchange). * Gall bladder concentrate the bile by NaCl and HCO3 reabsorption where as water reabsorbs isosmotically. bile pigment(bilirubin). than Ductal cell modified it by secreting HCO3 and absorbing Cl. Pancreatic duct is permeable to H2O so make it isosmotic.

* Endopeptidase hydrolyze interior peptide bond. vs.H+ exchange. VITAMINS :. 4.Ca++ absorption depend on active vit D (1. * Abetalipoproteinemia is failure to synthesize Apoprotein  results in inability to transport Chylomicron out of cell. absorptive mechanism is in Villi.channel (via cAMP) and Na+ follow Cl.Absorbs as fatty acid.Absorbs as a AA.K pump   IC Na+ conc on basolateral side. (apoprotein is one of the constituents of chylomicron). Cl diffuse passively by paracellular route. * Na+ .1. NaCl cotransport. stomach breaks lipid into droplets and intestinal bile emulsify it. cholesterol ester hydrolase & phospholipase A2 hydrolyze lipids into fatty acid. IRFAN MIR MD. * Intestinal cells reesterified Triglycerides.25 dihydroxycholecalciferol). * Dipeptide & Tripeptide absorbs faster than free AA due to 4 separate carriers for acidic. NaCl co transport 2.  Leaky (permeable) junction present in epithelium of small intestine and gall bladder. * Pancreatic protease degrade each other and also absorbed along with dietary protein. (Glycerol is hydrophilic & is not contain in micelles) * Lingual Lipase digest some lipids. monoglycerides & cholesterol in the form of micelles. Na+ . Na+ AA co transport. * PH for pepsin is 1 – 3. * Ca++ :. * Pancreatic lipase.absorption accompanies Na+ absorption through out the GI tract by -. Cl .HCO3 exchange 3.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. Dipeptide and Tripeptide in intestinal cell. Diarrhea. Exopeptidase hydrolyse one AA at a time from C terminal . * Cl is primary ion secreted in intestinal lumen through Cl.Coli toxin activate adenylate cyclase at the basolateral mem of the crypt   IC cAMP   Cl secretion  Na+ and H2O follow Cl. 2.  PROTEIN -. Tight Junction are  Tight (impermeable) junction present in epithelium of colon. * Cl.Secretive mechanism is located in Crypt.Occur by cellular and paracellular routes. Where as colon is less permeable to water.Fat soluble vit absorbs along with lipid and water soluble vit absorbs with Na+ cotransport where as VitB12 together with Intrinsic factor absorbed in ileum. In Intestine cells Heme iron broke down to release iron which bind to Apoferritin and transport to blood than In blood it bound with Transferrin which take iron to liver and store it. * H2O absorbs in small intestine and gall bladder osmotically. Passive diffusion (Na+ channel) 3. basic. NaCl absorption ------. neutral & Imino AA absorption. SECRETION OF ELECTROLYTE AND H2O :. (Iron deficiency is the most common cause of anemia) ------------------------------------------------------------------------------------ 14 . * Dipeptide and Tripeptide must hydrolyse by cytoplasmic peptidase to AA prior to enter into the blood. (  vit D cause Rickets and Osteomalacia ) * Iron :. ABSORPTION OF ELECTROLYTE AND WATER :. monoglyceride & chlesterol. * In colon Na+ channel are stimulated by Aldosterone. vs. PH more than 5 inactivate pepsin as in duodenum. * Pepsin secreted as pepsinogen from Chief cells H+ converts it into pepsin. * Free AA. eg Tripsinogen is converted to Trypsin (active form) by Enterokinase in small intestine. * Cholera toxin some E.1. phospholipids with cholesterol and apoprotein form chylomicron & than chylomicron transported out of cell by exocytosis in the lymphatics later chylomicron added to the blood via thoracic duct.where as water follow them.Iron absorbes as heme iron ( bound to hemoglobin or myoglobin ) or as a free Ferrous (Fe++). * K+ absorbs by passive diffusion (via paracellular route in small intestine) where as K+ secreted actively by aldosterone in colon In diarrhea K+ secretion is  in colon  hypokalemia. Na+ glucose.  LPIPDS -. Pepsin is not essential for protein digestion * Pancreatic protease are secreted in inactive form which is activated by brush border enz. * Hyper secretion of gastrin   H+ secretion   PH in duodenum  Inactivate pancreatic lipase  Statorrhea. Dipeptide and Tripeptide absorb with Na+ as sec active transport than AA enters blood by facilitated diffusion.

HCO3).  Hyperosmotic Vol Expansion  NaCl intake    Hct  .200 mmHg (auto regulation). (300-350mg/dl) * At 300 . * GFR is measured by Inulin clearance because Inulin is filtered but not reabsorbed or secreted by renal tubules. fever. GFR = Kf [ ( PGc . 15 .Plasma. * Rena clearance can be measured by C = UV/P RPF = c PAH = [U] PAH V / [P] PAH * GFR is 20% of renal plasma flow (RPF) 125ml/min.0 * If TF/PNa+ is < 1 Net Reabsorption of solute occur  dilution of TF.amount excreted / conc in plasma. It  by  in protein conc   GFR.¼ of ECF or 1/12 of TBW & is measured by radioiodinated serum albumin RISA or evan blue. * Threshold at which glucose first appear in the urine is approx 300 mg/dl. * PBc : -.Na+  .ECF. Na - Isosmotic Vol Contraction Diarrhea  No change No change  Hct . * Tm CURVE FOR PAH :.  Hyposmotic Vol Expansion SIADH    Hct (RBC swell). * RBF remain constant over the range of arterial BP from 100 . * TBW -. Na+   Hyposmotic Vol Contraction Adrenocortical insufficiency (loss of NaCl)     Hct. ------------------------------------------------------------------* RBF (renal blood flow) is 25% of cardiac out put. * If TF/PNa+ is > 1 secretion of solute occur  produce concentrated TF. * Filtration Fraction is the fraction of RPF that filter across the glomerular capillaries ( it is 0. Filtration Fraction = GFR / RPF * GFR can be expressed by Starling equation.glucose co transport. by constriction or blockade of ureter   GFR. It  by dilatation of afferent arterioles & by constriction of efferent arterioles. * Secretion of PAH from Peritubular capillaries into tubular fluid occur in proximal tubule. * Both BUN and Plasma Creatinine  as GFR . along the length of glomerular capillaries. ( TBW vol is measured by Titrated H2O or D2O) * ICF -. IRFAN MIR MD. * Bc : -.KICK THE BOARDS “USMLE STEP 1” RENAL AND ACID BASE PHYSIOLOGY Prepared by Dr.60% of body wt.Plasma glucose conc of < 300 mg/dl can be absorbed by proximal tubule through Na . (it contain Na+. * Na+ REGULATION: Na+ in the tubular fluid (TF) in Bowman space equals that in plasma (P) is said to be TF/ PNa+ = 1.is zero small amount usually absorbs * NaCl and Mannitol donot cross cell mem and confined to ECF. Mg++. ATP etc) * ECF --1/3 of TBW and is measured by sulfate.( Gc - Bc) ] * PGc : -. * Gc :-. or manitol. * RPF (renal plasma flow) measured by PAH clearance because PAH is both filtered and secreted by renal tubules.20). Serum Na+ ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Isosmotic Vol Expansion Isotonic Nacl infusion  No change No Change  Hct .is constant along the length of capillaries. inulin.(it contain Albumin and Globulin etc) * Interstitial fluid --. * Fluid Compartment -.spilling of glucose occur in urine before saturation or (Tm) Transport maximum. Protein. Na - Hyperosmotic Vol Contraction Sweat.PBc) . (RBC swell) Na+ .2/3 of TBW and is measured by TBW . GFR = [U] inulin V / [P] inulin. ( it contain K+.PAH filtration  as PAH plasma conc . ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------TYPE EXAMPLE ECF Vol ICF Vol ECF Osmolarity Hct.¾ of ECF ( ¼ of TBW ) and is measured by ECF . * Plasma -. Cl-. * SPLAY is the region of glucose curve b/w Threshold and transport max. * Relative Clearance: PAH > K+ > inulin > urea > Na+ > glucose > AA > HCO3-.350 mg/dl --. Inorganic ph.is measured by vol = amount injected . * PAH secretion  when plasma conc  once carriers become saturated it stops further  in secretion due to Tm. thus 20% of RPF is filtered. * RPF is measured at plasma PAH conc below the Tm (Transport max). ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- * TRANSPORT MAX CURVE FOR GLUCOSE :. Diabetes Insipidus    Hct (RBC shrunk) Na+ . * More water than salt lost during sweating.

* TF/PK+ = 1 in Bowman space. SHIFT OF K+ b/w ECF AND ICF -----------------------------------------------------------------------------------------------------------------------------------------------------------------------Causes of K+ shift out of cell ( hyperkalemia) Causes of K+ shift into the cell (hypokalemia) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------* Insulin Deficiency * Insulin *  adrenergic antagonist *  agonist * Acidosis ( via H+ . * Only 1% of filtered Na+ is excreated. * Na+ is reabsorbed by Co transport with glucose. * PT reabsorb 67% of K+ alonge with Na+ and H2O.phosphate Cotransport.H+ exchange in PT. * Distal tubule and Collecting duct together reabsorbe 12% of filtered Na+. * Principle cell reabsorb Na+ & secrete K+ in late distal tubule (DT) & collecting duct.Cotransport also called diluting segment and is impermeable to H2O (loop diuretics act here).K+ is filtered. * Starling forces in peritubular capillaries (due to  or  in protein conc)   or  in proximal tubular reabsorption. IRFAN MIR MD.K+ exchange) * Hyperosmolarity (H2O out of cell K+ follow) * Hyposmolarity (H2O flow into the cell K+ follow) * Na+ . * Na+ absorbed with Cl. * K+ REGULATION :. ( Tx of hypercalcemia ) * Thiazide  Ca++ excretion by reabsorbing Ca++ in distal tubule ( Tx of Hypercalciurea ). AA. * Mg++ Regulation : Reabsorb in PT. * PTH  Ca++ reabsorption in DT.K+ exchange ) * Alkalosis ( via H+ . ( PTH also  bone resorption ) * phosphate is urinary buffer for H+  excretion of H2PO4 (titrableacid).K+ . (Aldosterone/ ADH act here) * Intercalated cell secrete H+ & reabsorb K+ in late DT & collecting duct.2Cl. * ADH  urea permeability of inner medullary collecting duct which contribute urea recycling in the medulla.Co transport. Thick ascending limb and DT * In Thick ascending limb Mg++ and Ca++ compete for reabsorption. * DT and Collecting duct reabsorb 9% of Ca++ actively. * Loop diuretics cause  Ca++ excretion by inhibiting Na+ reabsorption.2Cl.Cl.K+ . * Na+ is reabsorbed also by Counter transport as Na+ . (total of 67% of Na+ reabsorbed in PT) * In Thick ascending limb of Loop of Henle 20% of Na+ reabsorbed as Na+ . K+ in proximal tubule.K+ pump inhibitor * Excersize * Cell lyses --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- EFFECT OF DISTAL K+ SECRETION --------------------------------------------------------------------------------------------------------------------------------------Causes of  distal K+ secretion Causes of  distal K+ secretion -----------------------------------------------------------------------------------------------------------------------------------------------------------------------* High K+ diet * Low K+ diet * Hyperaldosteronism * Hypoaldosteronism * Alkalosis * Acidosis * Thiazide * K+ sparing Diuretics * Loop diuretics * Renal failure * Luminal Anion -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- * Urea Regulation : 50% of urea reabsorb passively in PT. lactate.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. * Ca++ Regulation : 90% of Ca++ reabsorbed in PT and Thick ascending limb of Loop of Henle. (Aldosterone also act here to secrete H+). Other segment are impermeable to urea.in middle and late PT. (Thiazide act here). * Thick ascending limb of Loop of Henle reabsorb 20% of filtered K+ as Na+ . * Phosphate Regulation : 85% of phosphate reabsorb in PT as Na+ .Cotransport. Where as 15% excreted. * Mild  in Mg++  stimulate PTH secretion   Ca++ reabsorption. * Early Distal tubule is Cortical Diluting segment reabsorb Na+ by Na+ . ph.( also  Phosphate reabsorption ) 16 . secrete & reabsorbed by nephron to achieve K+ balance. * Severe  in Mg++  inhibit PTH secretion   Mg++ reabsorption. * PTH Inhibit phosphate reabsorption  phosphaturia &  urinary cAMP. * Distal Tubule and collecting duct either reabsorb or secrete K+ depend on dietary intake.

* ECF vol expansion   HCO3 Reabsorption . (Contributing to Contraction Alkalosis) ----------------------------------------------------------------------------------------------* H+ secrete in the lumen by H+ . [ TF/Plasma osmo = <1 ] * Early distal tubule is cortical diluting segment and is impermeable to H2O. ATP. ADP.H+ exchange in PT (stimulate Aldosterone synthatase)  HCO3 reabsorption in PT ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Guanylate cyclase cGMP IP3 mech ACID BASE BALANCE : * Buffer prevent changes in the pH when H+ ions are added or removed. * PH = pK + log [A-]/ [HA-] . IRFAN MIR MD.8) * Major IC buffer is Hg.is base of the buffer and HA. Deoxyhemoglobin is Better buffer than Oxyhemoglobin at physiologic pH. * Thick Ascending loop of henle reabsorbe Na+ . (pK of CO2/ HCO3 buffer is 6.Intercalated cell  GFR.2Cl by cotransport & is permeable to H2O. * Secreted H combine with filtered HPO4  H2PO4 (titrable acid).and A-. * Vasa Recta (capillaries of Loop of henle) maintain the corticopapillary gradient by serving as osmotic exchanger. HORMONES THAT ACTS ON KIDNEY: --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Hormnes PTH Stimulus for secretion  Plasma Ca++ mild  in Mg++  Plasma Osmolarity  Blood vol  Blood vol (via renin AT)  Plasma K+  Atrial Pressure  Blood vol (via renin) Time course Fast Mech of action Adenylate Cyclase cAMP (at basolateral side) Adenylate cyclase V2 Receptors New Protein Synthesis Action on kidney  ph reabsorption (PT)  Ca++ reabsorption (DT) Stimulate 1  hydroxylase in PT  H2O permeability in late DT & collecting duct (principle cell)  Na Reabsorption in DT.  Na+ reabsorption --------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ADH Aldosterone Fast Slow ANF Angiotensin Fast Fast  Na+ .ATPase and resultant HCO3 is reabsorbed. Here H2O reabsorb normally untill TF/Plasma Osmo >1 .Principle cell  K secretion in DT . * Minor IC buffer is organic Phosphate (AMP. Here H2O reabsorb normally until TF/Plasma Osmo = 1 * In collecting duct H2O permeability  by ADH.is acid of the buffer) RENAL ACID BASE : * Filtered HCO3 reabsorbs in proximal tubule in two steps *  PCO2   HCO3 Reabsorption ( because IC H+ is  ) *  PCO2   HCO3 Reabsorption ( because IC H+ is  ) * ECF vol contraction   HCO3 Absorption (contraction Alkalosis) and produce acidic urine. ( Buffer is most effective in the linear portion of the titration curve. * Angiotensin II stimulate Na+ H+ exchange   HCO3 reabsorption.Principle cell  H+ secretion in DT . * Another mech for excreting H+ is NH3 Production in renal cell from glutamine. * Major EC buffer is HCO3.0 pH unit of the pK. 2. * CONC AND DILUTION OF URINE :* Corticopapillary osmotic gradient : * Is the gradient of osmolarity from cortex ( 300 mOsm /L) to papilla (1200 mOsm /L) & is comprise primarily of NaCl & urea.3 DPG) * When pH of the solution is equal to pK than there are equal conc of HA. ( NH3 production  in Acidosis which favor H+ excretion ) H+ + NH3  NH4+ excreted in urine (diffusion trapping) 17 .K+ . (where A. * In late distal tubule H2O permeability  by ADH. This Process results into net excretion of H+ in urine.1) * Minor EC buffer is Phosphate (PK of H2PO4 /HPO4 2 buffer is 6.) * Buffer are more effective with in 1.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr.

Vol of conducting airway it is 150 ml normally.Vol that remains in the lung after max expiration. Inspiratory Reserve Vol (IRV) -. Functional Residual Capacity (FRC) = Expiratory Reserve Vol + Residual Vol 3. Vital Capacity = Tidal Vol + Inspiratory Reserve Vol + expiratory Reserve Vol 4. ( cant be measure by spirometery ). ACID BASE DISORDER: --------------------------------------------------------------------------------------------------------------------------------------DISORDER Metabolic Acidosis CO2 + H2O   H  + HCO3  Resp Compensation Hyperventilation Renal Compensation -------------------------------------------------------------------------------------------------------------------------------------- H+ excretion  HCO3 reabsorption Metabolic Alkalosis    Hypoventilation  HCO3excretion Respiratory Acidosis    None  H+ excretion  HCO3 reabsorption Respiratory Alkalosis    None  H+ Excretion  HCO3 reabsorption ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------* RULE : CO2 goes up HCO3 goes up CO2 goes down HCO3 goes down. ( measured by Bohr’s Method ) * Minute Ventilation = Tidal Vol  Breath / min * Alveolar ventilation = Tidal Vol  Dead space  Breath / min * LUNG CAPACITIES : 1. * MUSCLE OF INSPIRATION : Diaphragm (normally) External Intercostal Muscle Accessory Muscle ( during exercise ) * MUSCLE OF EXPIRATION : Passive (normally) Abdominal & Internal Intercostal muscle ( during exercise ) (can not measured by spirometery) * COMPLIANCE :-The extent to which lung expand (stretchability) for each unit in Transpulmonary P is called the Compliance.is the vol that can be expired after expiration of the tidal vol. 4. * Forced Expiratory Vol (FEV): Is air expired in one Second after Max Inspiration. 3. (measured by Fowler’s Method ) * Physiologic Dead space -.16 mEq / L.  Compliance   Stretchability where as  compliance   stretchability. 2. FVC. Normal Serum Anion Gap is 10 . ( Compliance measures stiffness of the lung ) ( Change in Intrapleural P during inspiration is used to measure dynamic compliance of the lung ) 18 .KICK THE BOARDS “USMLE STEP 1” Prepared by Dr.is the vol inspired and expired with each normal breath.is the vol that can be inspired over the tidal vol eg during exersize. IRFAN MIR MD. Total Lung Capacity = Tidal Vol + IRV + ERV + RV. Tidal Vol -. Residual Vol (RV) -. * Anatomic Dead space -. ( Serum Anion Gap = [Na+] . Expiratory Reserve Vol (ERV) -.vol of the lung does not eliminate CO2 normally or due to dis. * H+ Excreted in urine as H+ + HPO4 -2  H2PO4 (Titrable acid) H+ + NH3  NH4+ (diffusion trapping) * ------------------------------------------------------------------------------------------------------------------------RESPIRATORY PHYSIOLOGY * LUNG VOLUMES : 1. FEV / FVC = 0. Inspiratory Capacity = Tidal Vol + Inspiratory Reserve Vol. It is 80% of forced vital Capacity.[HCO3-] ) * Synthesis of Glucose (gluconeogenesis) during prolong fasting also occur in kidney. 2.[Cl-] .8 * In restrictive Lung Dis ( Fibrosis ) both FEV and FVC is reduced. ( Directly proportional relationship). * In Obstructive Lung Dis ( asthma ) FEV reduces more than FVC.

* Viscosity & Density changes the resistance to air flow : If density of gas   resistance to airflow  If density of gas   resistance to airflow  (breathing low density gas like helium) * Medium size bronchi are major site of resistance.Airflow is directly proportional to pressure difference of the mouth and alveoli and inversely proportional to airway resistance . 2.  Lung Vol exert less traction &  airway resistance For example in Asthma pt learn to breath at high lung vol to off set the high resistance. 3. During Expiration --. P gradient cause air to flow into the lung. During forced expiration Intrapleural P become +ve Lung vol return to FRC before another cycles begin. l is length of airway.ve and lung Vol  by 1 tidal vol (+ FRC).ve ( can be measured by baloon catheter in esophagus ) where as Lung vol is FRC. (Airflow) Q = P/R ( where P is pressure gradiant and R is Airway Resistance) * Airway Resistance (R) is describe by Poiseuille’s Law . --------------------------------------------------------------------------------------------------------------------------------------* Causes of  Lung Compliance * Causes of  Lung Compliance --------------------------------------------------------------------------------------------------------------------------------------High Expanding Pressure  Pulmonary venous return Fibrosis Lack of surfactant Emphysema ( Elastic fiber) Age --------------------------------------------------------------------------------------------------------------------------------------------------------------------------* Under equilibrium condition lung have a tendency to collapse which is exactly balance by tendency of chest wall to spring out. * HYSTERESIS :. Intrapleural P become more . * Small size airway do not offer  resistance because of parallel arrangement. * Compliance of the lung chest wall system is less than the lung alone or chest wall alone. Irritants. * Surfactant is made by Type II alveolar cells consist of Dipalmitoyl Phosphatidyl Choline. * In Emphysema lung compliance is  so FRC  too. * Factor that change Airway Resistance : * Parasym stimulation. so the lung chest wall system seek for higher FRC in order to balance these two forces again.( At rest before inspiration begin) 1. vs. IRFAN MIR MD. * SURFACE TENSION OF ALVEOLI AND SURFACTANT : * Tendency to collapse alveoli is directly proportional to the surface tension and inversely proportional to alveolar radius called Laplace Law .KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. 19 .* Diffusion of gases such as O2 and CO2 depends in the partial P difference across the mem and area available for diffusion. R = 8nl /  r4 Where n is viscosity of the inspired air. * Neonatal RDS cause by lack of surfactant  Atelactasis (difficulty in reinflation due to  compliance)  Hypoxemia (V/Q mismatch).Inspiratory muscles contract  thorax Vol to .Alveolar P become greater (+ ve) than atmospheric P. Intrapleural P return to its resting value during normal expiration (passively). This is the reason pt develop barrel shape chest to provide new Vol to lung with results into  O2 diffusion. * Surfactant lines the alveoli and reduce the tension   compliance. ----------------------------------------------------------------------------------------------- (eg deep sea diving) BREATHING CYCLE :.Is inflation of the lung follow different curve than deflation of the lung. ( In COPD airway resistance is  & pt expires slowly with pursed lip to prevent airway collapse which occur with forced expiration ) * Gas Exchange :. * AIRWAY RESISTANCE :. ( large alveoli has low tendency to collapse than smaller alveoli ). and r is radius of airway.Alveolar P equals atmospheric P ( alveolar P is said to be zero ). ( Can be measured by Dalton’s Law Partial P = Total P  Fractional concentration ). Slow reacting subs of anaphylaxis (constricts airway)   radius and  resistance * Sympathetic stimulation dilates airways   Radius and  Resistance (via 2 receptors). This change disturb the lung chest compliance system. Intrapleural P is . At Rest --. During Inspiration -. *  Lung Vol exert more traction (pulling force) &  airway resistance.

 PH. CHANGE IN O2 DISSOCIATION CURVE : 1. * Diffusion of O2 from alveolar air to pulmonary capillaries bed is usually perfusion limited but become diffusion limited in dis.( 90% . * Ferrous (Fe2+) state of iron bind O2 Where as ferric (Fe3+) state of iron is methemoglobin and does not bind O2. 20 . Temp. * In lung all above reaction occur in reverse ( which is HCO3.major form ) 2. * Cardiac output (pulmonary) is equal to systemic circulation. Where as in Emphysema diffusion of O2  because surface area for diffusion is .3 diphosphoglycerate (DPG) bonds less avidly to fetal Hg. PH. Shift to the Left --. ( that is why O2 movement from mother to fetus is facilitated ).When gas equilibrate early along the length of pulmonary capillaries the partial P of arterial blood become equal to partial P of alveolar air.100 mmHg. * About 2% of Cardiac output bypass pulmonary circulation because of physiologic shunt that’s why mixture of the venous blood makes PO2 of arterial blood slightly less than alveolar air.enter into RBC in exchange for Cl.3DPG).is exchanged for Cl.When the gas does not equilibrate fully by the time blood reaches the end of the pulmonary Capillaries the partial P of arterial blood is less than that of alveolar air .3DPG which bind to  Chain to facilitate unloading of O2 in tissue. * O2 affinity of fetal Hg is higher than adult because 2. Shift to the right --.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. *  PCO2 and  PH  the affinity of Hg for O2 & facilitating the unloading of O2 in tissue as in exercise.than HCO3combines with H+  H2CO3 which further decompose into CO2 and H2O and CO2 is diffuse out ). Dissolved CO2 ( small amount ) * CO2 generate in tissue  enter into venous plasma  enter into RBC where CO2 combine with H2O by Carbonic anhydrase  H2CO3  H+ and HCO3-. the human can tolerate change in atmospheric P without compromising the O2 carrying capacity of Hg.3DPG.  2. * At PO2 of 40 mmHg  75% of Hg is saturated. * Pressure and Resistance in pulmonary circulation is much lower than systemic circulation. By  the affinity of O2 . (Causes are PCO2. Eg In Fibrosis diffusion of O2  because of thickening of the alveolar mem   diffusion distance.  Temp.3 ml/100ml of blood . -----------------------------------------------------------------------------------------------O2 TRANSPORT : * Hg contain 4 subunit 2 and 2 ( each subunit contain heme moiety which is iron containing porphyrin ) . IRFAN MIR MD. * At PO2 of 25 mmHg  50% of Hg is saturated. ( Bohr’s Effect ) 2. * The affinity of 4th O2 molecule is very high. * Causes are  PCO2.  2. CO2 TRANSPORT : CO2 carried to the lung in 3 Forms. * Solubility of O2 in the blood is 0. * Because the curve is almost flat in PO2 range from 60 .Affinity of Hg to the O2   P50   unloading of O2 in tissue is more difficult . Carbaminohemoglobin ( small amount ) 3. * Diffusion limited exchange --. * Adaptation of chronic Hypoxemia (high altitude)   2. HCO3. Hg O2 DISSOCIATION CURVE : * At PO2 of 100 mmHg  Hg is almost 100% saturated. * In fetal Hg  chain is replaced by  chain.Affinity of Hg for O2   P50  . * H+ is buffered inside RBC (Deoxyhemoglobin) where as HCO3. Blood gases value in normal conditions: --------------------------------------------------------------------------------------------------------------------------------------------------------------------------Gas Dry Inspiration Humid Inspiration Alveolar Air Sys Arterial Blood Mixed Venous Blood --------------------------------------------------------------------------------------------------------------------------------------PO2 160 mmHg 150 mmHg (due to H2O in air) 100 100 % (slightly less) 40 mmHg PCO2 0 40 mmHg 40 mmHg 46 mmHg ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- * Perfusion limited exchange --.by RBC (Cloride shift). 1.

DISTRIBUTION OF PULMONARY BLOOD FLOW --.located in the lower pons .  Ventral Respiratory Group control Expiration & is not active during normal breathing because Expiration is passive . eg Metabolic Acidosis  the breathing rate ( where PCO2 is low). Pneumotaxic Center --------. * V/Q is highest ( > 1. So when CO2 enter CSF combine with H2O  H2CO3  H+ + HCO3(by carbonic anhydrase) than liberated H+ can act directly on central chemoreceptors.Distribution of pulmonary blood flow effect by gravity. PCO2.Breathing can be under voluntary control.8 ( 0. It inhibit inspiration therefore regulate inspiratory Vol and rate. It is imp in lung because local vasoconstriction divert blood from poorly ventilated area to well ventilated area. 2. * H+ ion stimulate carotid bodies chemoreceptors directly and is independent of PCO2 . ( with first breath alveoli become oxygenated and vascular resistance decreases ) * Both ventilation and Perfusion is great in base than in apex. CO2. 3. * H+ does not cross the BBB but CO2 does. Normal V/Q Ratio = 0. At base ---. More than 2% is Usually due to congenital abnormality   in arterial PO2.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. J Receptors located in alveolar wall close to capillaries it stimulated by capillaries engorgement as in LHF  Rapid shallow breathing. IRFAN MIR MD. 2. Medullary Resp Center:Dorsal Respiratory Group control inspiration & generate basic rhythm of breathing receive input from lung via vagus & from peripheral chemoreceptor via glossopharyngeal nerve where as it send output to diaphragm via pherenic nerve . * In fetus pulmonary vascular resistance is very high due to generalized hypoxic vasoconstriction as a result blood flow through fetal lung is low . ( that’s why  or  in CO2 cause change in breathing). BLOOD FLOW IN LUNG ZONES :  Zone 1 -. OTHER RECEPTORS THAT CONTROL BREATHING RATE : 1. Apneustic center ------------. Perfusion is normal and ventilation is Zero  No Gas Exchange.located in the upper pons. (stimulate by  PO2.Arterial P > Alveolar P > Venous P (blood flow is medium).0 ) in the apex of the lung and lowest ( 0. 21 . * Hypoxia cause local vasoconstriction (Opposite effect of that in systemic circulation where hypoxia cause vasodilation) . * In supine position blood flow is uniform through out the lung where as standing position blood flow is lowest in apex. Peripheral chemoreceptors present in Carotid and Aortic bodies.  Zone 3 -.V/Q  . (Apneusis) 3. Joint and Muscle Receptor   Breathing during (early) exercise. Cortex ------------------------. 3.In Hemorrhage)  Zone 2 -. V/Q is Zero when airway is completely blocked. Lung Stretch Receptors ( Hering Breuer Reflex ) stimulate by distention of lung   in breathing rate.PO2  and PCO2  2.Arterial P > venous P > Alveolar P (blood flow is highest) -.PO2  and PCO2  ---------------------------------------------------------------------------------------CONTROL OF BREATHING :1.8 when tidal Vol & pulmonary cardiac out put are normal. At apex ---. H+) * When Partial PO2 falls < 60 mmHg   breathing rate by peripheral chemoreceptors. It stimulate by noxious stimuli eg ammonia.8 ) at the base of the lung. Irritant Receptors located in b/w airway epithelial cells. 4. ? (very imp to understand) * Right to left shunt normally occur to a small extent because 2% cardiac output by passes the lungs. ---------------------------------------------------------------------------------------CHEMORECEPTORS FOR O2. * When PCO2    in breathing rate. ( Alveolar P collapses the capillaries when arterial BP is low eg . It stimulate inspiration more deeper and prolongs Inspiratory gasp. Where as Left to right shunt   in venous PO2 (donot result in a  in arterial PO2) VENTILATION / PERFUSION RATIO : 1. 2.Alveolar P > Arterial P > Venous P (blood flow is lowest) -.V/Q . V/Q is Infinity when blood flow is blocked and ventilation is normal  No Gas Exchange. 4. and it is liable for 100 mmHg of PO2 & 40 mmHg of PCO2). (imp to understand) * PO2 is greater than PCO2 in different region of lung. Central Chemoreceptors of the medulla is sensitive to PH of CSF. & H+ :1. smoke etc. 2. 1.

Pulse P : is difference b/w systolic and diastolic P and is determined by stroke Vol ( stroke Vol   Pulse P  )  in capacitance (compliance) such as with aging results in  Pulse P. Q = P/R (Q= Flow. It is starts from beginning of P wave till the beginning of Q wave. * PH stays normal during moderate exercise where as PH  during strenuous exercise due to lactic acid production.21 QRS complex -. T wave -. * Pulmonary vascular resistance  (vasoconstriction).  affinity of Hg for O2 and facilitate unloading O2. Diastolic P : is the lowest arterial P during cardiac cycle (heart relaxes) 3. v = Q/A * Blood flows from high P to low P & is inversely proportional to resistance of the blood vessel. * Largest fall of P occur across the arterioles since arterioles are the site of the highest resistance. Compliance  as person ages. * Pulmonary blood flow .is beginning of Q wave till the end of T wave.12 QT interval -.is Ventricular Depolarization it also buried Atrial Repolarization. IRFAN MIR MD. 1. (produce bruits ) * Capacitance ( compliance ) describes the distensibility of the blood vessels & is directly proportional to Vol & inversely proportional to P. NL time 0. * Capillaries comprise of largest total cross sectional area and surface area.Atrial depolarization ( shows the size and thickness of atrium) PR interval -. Normal time 0. C = V/P ( V is volume where as v is flow ) * Compliance is much greater in arteries. ELECTROCARDIOGRAM : P wave -. * Hg O2 dissociation curve shift to the right side (Bohr’s effect). V/Q rate more evenly distributed through out lung ADOPTATION TO HIGH ALTITUDE : * Alveolar PO2  and Arterial PO2 also . polycythemia)  the renold No  turbulence.41 ( shows the size and thickness of ventricle) ST segment -. It represent entire depolarization & Repolarization of ventricle.3 DPG conc  ( facilitate unloading of O2 in tissue ). It is isoelectric period shows entire ventricular depolarization. ( Compliance   Pulse P  ) * Blood flow P falls over its course due to changing resistance of vessels (that’s why P is highest in aorta than in vena cava). INTEGRATED RESPONSE OF RESPIRATORY SYSTEM DURING EXERCISE : *  O2 consumption and CO2 production *  ventilation rate * No change in arterial PO2 and PCO2 where as Venous PCO2 . Normal time 0. * Arterial PH  (  Respiration cause Alkalosis ) * Hg conc  ( because  erythropoietin production ) * 2. (PR interval  when conduction velocity is slow due to heart block).Interval b/w atrial depolarization & ventricular depolarization. * Ventilation rate .  Hematocrit)  the Renold No  Turbulence. in narrowing of vessel. ( produce audible bruits )  Blood viscosity (eg. As renold No  the tendency of turbulence.  Blood viscosity ( due to anemia. Systolic P : is highest arterial P during cardiac cycle (heart contracts) 2.is ventricle Repolarization. 22 .( Compliance   Pulse P  ) 4. R = 8l /  r4 (  is viscosity and l is length of vessel ) * Renolds No: Renolds No predict whether flow is laminar or turbulent. ----------------------------------------------------------------------------------------------------------------CARDIOVASCULAR PHYSIOLOGY * Stress Vol is the blood in systemic arteries which are thick walled.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. * Unstress Vol is the blood in systemic veins and have lowest P.Is segment from the end of S wave till the beginning of T wave. * Velocity of blood flow is directly proportional to blood flow & inversely proportional to cross sectional area. * Arterial Pressure is pulsatile and not constant during cardiac cycle. Mean Arterial P: is average Arterial P with respect to time calculated by Diastolic P + 1/3 of Pulse P. A= area) * Resistance is directly proportional to the blood viscosity & length of the vessel and inversely proportional to the 4th Power of the vessel radius ( Poiseuille’s Law ). * Arterioles are the site of high resistance and is innervated by autonomic fibers.

3. inward Na+ conductance called I###. troponin. 1. (  IC Ca++  Ca++ triggered Ca++ release from SR ) 23 . * . Phase 4 : Resting mem potential ( inward outward current is equal ). ----------------------------------------------------------------------------------------------MYOCARDIAL CELL STRUCTURE : * Sarcomeres is the contractile unit of myocardial cell it runs Z to Z. SA node. Absolute Refractory period : Begins with Action potential & end after Pleateau. * . * Dromotropic Effect : is  or  of conduction velocity by slowing or speeding the conduction through AV node. ( I### turn on by Repolarization ) Phase 0 : Up stroke of action potential cause by  inward Ca++ flow ( it derive mem potential toward Ca++ equilibrium potential ) Phase 3 : Repolarization (caused by  outward K+ conductance) * Phase 4 account for the pace maker activity of the SA node automaticity ( Note -. tropomyosin) * Intercalated disc present at Z and maintain cell to cell cohesion. (Ventricle filling may be compromised). and AV node have parasympathetic innervation but ventricle do not. * + ve dromotropic effect  the conduction velocity through AV node   in PR interval. contain thick filament (myosin) & thin filament (actin. IRFAN MIR MD.ve chronotropic effect  the HR by  the rate of Phase 4 depolarization. during the course of action potential changes are describe as Refractory Period. Phase 4 : Slow depolarization -. conducted action potential can not be elicited. It can over ride SA node if SA node is not functioning. Phase 2 : Transit  in inward Ca++ flow &  outward K+ flow result in Plateau (outward & inward current are approx same during this period) Phase 3 : Is repolarization in which inward Ca++ conductance  and outward K+ conductance . Cardiac AP: Na . the mech is  in I### (  in Na+ conductance ). * The intrinsic rate of Phase 4 depolarization (heart rate) is slower in AV node and HIS purkinji system than in SA node. Relative Refractory period : Period followed by ARP when repolarization is almost complete. Conduction velocity depend upon size of inward current during up stroke. the mech is  in I### (in Na+ conductance). Resting mem potential is determined by conductance to K+ and approaches K+ equilibrium potential. and are low resistance pathway b/w cells. ----------------------------------------------------------------------------------------------AUTONOMIC EFFECT ON HR & CONDUCTION VELOCITY : * Chronotropic Effect : is  or  of HR by  or  firing of the SA node. * + ve chronotropic effect  the HR by  rate of Phase 4 depolarization. * The magnitude of tension develop in heart is proportional to the  in IC Ca++.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. (account for electrical syncytium) * T tubules continuous with cell mem ( it carries action potential ) well develop in ventricle and poorly develop In atria. AP can be elicited but more than usual current is required.  inward Na flow  depolarization (at the peak of AP the mem potential is equilibrium potential for Na+). AP cannot be elicited during this period. (AP are of longer duration in ventricle 300 m sec) Phase 0 : Up stroke.K ATPase maintain ion gradient across cell mem.ve dromotropic effect  the conduction velocity through AV node   PR interval. 2. Phase 1 : Initial repolarization caused by  inward Na+ flow and initial K+ outward flow ( it is brief period ). * The Atria. * Gap Junction present at intercalated disc.Phase 1 & 2 are not present in SA node action potential ) Conduction velocity is the time required for exitation to spread in the heart it is fastest in purkinji system and slowest in AV node (this is the reason EKG shows PR interval). Sinoatrial Node (SA) : * It is Pace maker and does not have resting mem potential ( it exhibit Phase 4 Depolarization ) * AV Node and HIS Purkinji system are latent pace maker.  outward K+ conductance hyperpolarize the mem (equal to K+ equilibrium potential) and than resting mem potential. EXITABILITY is ability of heart to initiate action potential response to inward current. * Sympathetic innervation is through out the heart. Effective Refractory period : Slightly longer than ARP.

----------------------------------------------------------------------------------------------CONTRACTILITY ( Inotropism ) : Is ability of cardiac muscle to develop force at given muscle length. Fig: VENTRICULAR PRESSURE . Quabain ).K+ ATPase  IC Na+ to   Inhibition of Na+ Ca++ exchange   IC Ca++ ) Eventually all three  the IC Ca++   contractility .myosin interaction by troponin . * Factor that  Contractility are Parasympathetic by  Ca++ entry into the cell ( . * It Can be measured by Ejection Fraction ( stroke vol / end diastolic vol ) which is normally 0.  HR (In +ve Stair case or Bowditch Stair case  in IC Ca++ occur over several beats & in Post extra systolic potentiation IC Ca++  due to accumulation ) 2.VOL LOOP : * A cycle of ventricular contraction. LENGTH TENSION RELATIONSHIP : * It describes the effect of ventricular cell length on the strength of contraction (similar in skeletal muscle). It is constructed by Diastolic and systolic Pressure curve. Cardiac Glycoside ( Digitalis.Vol loop . * Relaxation occur when Ca++ is reaccumulated in SR by active Ca++ ATPase pump. ( Velocity of contraction  by  in after load ) Fig: FRANK SRATLING RELATION SHIP : Is based on length tension relation ship. * Ca++ binds Troponin C to remove inhibition of actin . relaxation. * Change in contractility shift Frank starling curve. via  Ca++ entry during plateau OR via  Ca++ pump activity in SR ( phospholambam ) 3. Sympathetic stimulation.ve inotropic effect ) * Factor that  Contractility ( + ve inotropic effect ) : 1.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. In other word it is a mechanism that matches Cardiac output and venous return. Fig: 24 . * Frank starling relation ship describes  in Cardiac output (stroke Vol) that occur in response to an  in venous P (end diastolic Vol ). * Preload is equivalent to End Diastolic Vol (  end diastolic vol   in fiber length   in developed tension ) * Afterload is equivalent to Aortic Pressure. ( digitalis Na+ .55 (55%). It  by  Aortic P. ejection.tropomyosin to cause contraction. IRFAN MIR MD. and refilling can be seen by combining of two curve into Pressure .

[O2] pul artery) Stroke Work = Stroke Vol  Aortic P * Stroke work is work done by heart and fatty acid is primary source of energy for stroke work. * Slope of the venous return curve is determined by resistance of the vasculature. IRFAN MIR MD. * Mean systemic P is equal right atrial P when there is no flow in CVS.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr.  TPR   venous return to heart vs. ---------------------------------------------------------REGULATION OF ARTERIAL PRESSURE : * FAST --. CARDIAC AND VASCULAR FUNCTIONAL CURVE : * Change in End diastolic is major mechanism of alteration in cardiac output. in IC Pressure  compression of cerebral blood vessel  cerebral ischemia   sympathetic out flow  contractility. Additional baro receptor present in Aortic arch which respond only to  in arterial P. Baro receptor (stretch receptor) respond fast and regulate minute to minute arterial BP. * A clock wise relationship of venous return curve indicate  in TPR which results into  venous return and cardiac output. size of heart.  TPR   venous return to heart.  HR. ( this is exactly opposite of . vasomotor center reduce it by  parasym vagal out flow to heart and  sympathetic out flow to the heart and blood vessels ( vasoconstriction). * AT II  vasoconstriction of arterioles (TPR) & stimulates Aldosterone secretion. (K+ &  blood vol also stimulate Aldosterone secretion ) * Aldosterone  Reabsorption of salt and water by distal tubules   blood Vol and mean arterial P. 2. Flow to other organ (eg kidney) significantly reduced  Renin. * Baro receptor mechanism present in carotid sinus located near bifurcation of common carotid artery respond to high or low BP. both parasympathetic & sympathetic outflow. * Cushing reaction -.Neurally mediated. *  Renal perfusion P  Renin release  Renin catalyze angiotensinogen to angiotensin I (in plasma) than angiotensin I is converted to AT II (in lung) by ACE.Renin angiotensin and Aldosterone respond slow.  AT II   TPR. * SLOW --. * When two curve intersects each other the point is called equilibrium or steady point. * Venous return & vascular functional curve shows relation ship b/w flow through the vascular sys & the right atrial P. * Cardiac functional curve shows frank starling relation ship for the ventricle. ( remember after load is  by  aortic P) Cardiac output = stroke Vol  HR (can also be measured by Flick's principle CO = O2 consumption / [O2] pulmonary vein . Whereas counter clock wise relationship indicate  TPR   venous return & cardiac output. (but not to  BP) * Baro receptor  the firing rate of carotid sinus nerve IX (glossopharyngeal) which carries information to vasomotor center in brain.  TPR with simultaneous reduction in Heart rate (Parasym). 25 . It shows shift of curve. Chemoreceptor in aortic and carotid bodies are very sensitive to hypoxia (because of very high rate of O2 consumption)  stimulate vasomotor center to restore BP. OTHER REGULATION OF ARTERIAL BLOOD PRESSURE : 1. Cerebral Ischemia -. It  or  by  or  in blood Vol. * Set point for the mean arterial P in vasomotor center is 100 mmHg so if set point .ve Inotropic drug ) *  or  in Blood Vol   or  in venous return and cardiac output. Fig: CARDIAC O2 CONSUMPTION :  by  afterload .  contractility. * Equilibrium occur when cardiac output equals venous return. * + Inotropic agent (digitalis) cause  in contractility →  in cardiac output which further lowers right atrial P . (that is why is very hard to control BP in CVA or strokes) Mean arterial P  to life threatening level.

Is  in blood flow to an organ after a period of occlusion to flow.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. Heart Reactive Hyperemia -. * BBB is a tight cleft b/w endothelial cells of capillaries.  in Pi oppose filtration out of the capillaries. Pc is higher at arteriolar end of the capillaries than venous end. * Control by local metabolites specially hypoxia and Adenosine  vasodilatation to  blood flow. large water soluble subs via pinocytosis. * Serotinin  arteriolar vasoconstriction. * Prostaglandins --. small water soluble subs. can be varied depends upon metabolic need. * Edema caused by excess filtration or blocked lymphatics or by  Pc. (Wheal is an edema results from local histamine release). Factor that increase filtration are  Pc. It release upon vessel damage and prevent blood loss. It  Pc & cause local edema. i ( Interstitial oncotic or colloid osmotic P) when  favor filtration out of capillaries. Skeletal muscle contraction also aid it. ( one form of EDRF is Nitricoxide ) * Ach  vasodialation by stimulation of EDRF production. Atrial natriuretic Paptide (ANP) release in response to  atrial P  dilation of arterioles (inhibit vasoconstriction). Remember capillaries do not have smooth muscles instead containing endothelial cells. ------------------------------------------------------------------VASOACTIVE HORMONES : * Histamine  arteriolar dilation & venoconstriction.( c .V1 receptors  cause vasoconstriction ( TPR) V2 receptors   reabsorption of water by distal tubule and collecting duct. 3. It also  salt & water excretion and inhibit Renin release. Pi. One way flap valve permit unidirectional lymph flow. 26 .When perfusion P   arteriolar smooth muscle stretches follow by contraction  vasoconstriction occur (by this maintain constant flow) Active Hyperemia -. IRFAN MIR MD. H+. Heart Vasodilator metabolites are CO2. (K  due to burn & inflammation) * EDRF (produce by endothelial cell) relaxes smooth muscle by Guanylate cyclase mech produce GMP. In intestine & liver these cell clefts are wide open called Sinosoids it allow protein to cross. &  TPR. Vasopressin (ADH) release in response to  blood Vol or P. * Bradykinine  arteriolar dilation and venous constriction it also cause edema. c. 3. eg .Is blood flow to organ proportional to its metabolic need.  c. ) FLUID EXCHANGE ACROSS CAPILLARIES : * It can be determined by Starling equation Jv = K [ ( Pc . ------------------------------------------------------------------* Flow through capillaries is regulated by contraction and relaxation of the arterioles and the precapillaries sphincters. ( 3 types of subs cross capillary wall 1.PGI 2 (prostacyclin) and PGE  vasodilation PGF  vasoconstriction TxA2  vasoconstriction CORONARY ARTERY CIRCULATION : 5% is resting cardiac output. i . Autocirculation -. c (Capillaries oncotic or colloid osmotic P) when  opposes filtration out of capillaries. lipid soluble subs. Except in glomerular capillaries where it is nearly constant. eg . ( Remember  arteriolar or venous P   Pc but  venous P has greater effect on Pc ) Pi (Interstitial fluid hydrostatic P) Normal Pi is 0mmHg . -------------------------------------------------------------------FUNCTION OF LYMPHNODE: * Excess filtered fluid is returned to circulation via lymph. 4. lactate and Adenosine. ------------------------------------------------------------------SPECIAL CIRCULATION :Blood flow is regulated by altering arteriolar resistance.Pi ) . 2.  K. K+. ADH act on --.i ) ] Jv is fluid flow and Kf is filtration coefficient Pc (Capillaries hydrostatic P) when  it cause net filtration.

* Adrenal medulla is a special case in which preganglionic fiber synapse directly on chromaffin cells of adrenal medulla it use ACh as NT & secret EN 80% & norEN 20% . * Symp ganglia are located in paravertebral chain where as parasymp ganglia are located in effector organ. (due to temporary compression of arterioles with resultant vasodilatation ) *  receptors cause vasoconstriction where as  receptors cause vasodialation. ----------------------------------------------------------------* Upon Standing (gravity)   in venous P. ADH . SKIN CIRCULATION : Is 5 % of resting cardiac output. SKELETAL MUSCLE CIRCULATION : Is 20 % of resting cardiac out put. IRFAN MIR MD. * Ventricle filling is divided into Rapid ventricle filling & Reduced ventricle filling (Diastasis) which is last part of ventricle filling curve. * Exhibit Autoregulation. NEUROPHYSIOLOGY * Autonomic nervous sys (symp. * Preganglionic symp fiber are short and synapse in autonomic (paravertebral) ganglia its cell bodies are present in CNS & Postganglionic symp fibers are long & synapse in effector organ & its cell bodies are located in Autonomic (paravertebral) ganglia. Reactive hyperemia occurs after that brief period of occlusion to replay the O2 dept. Adenosine. (Mechanical Effect) * Sympathetic nerev play a minor role. * Parasymp receptor in effector organ is Muscarinic but in skeletal muscle (somatic) is Nicotinic. * Inspiration split the second heart sound. * Parasym and Symp receptors in ganglion are Nicotinic and NT is ACh.  Pc   Filtration  initial  in stroke vol & cardiac output  compensatory mech starts (via carotid baro receptors)  HR . parasymp & enteric) is distinct from Somatic nervous sys which innervate skeletal muscles and use ACh as a NT where as receptor is nicotinic. * During systole mechanical compression of the coronary vessel reduces blood flow. * Local metabolites like lactate. Arterial P  (slightly). * Mechanical effects compensate by reactive hyperemia. * Skin have extensive sympathetic innervation and flow of blood is in extrinsic control (temperature regulation). Renin . * Control by local metabolites specially CO2  ↑ or ↓ of pH  vasodilatation of cerebral arteries to  blood flow. splanchnic & cutaneous vascular bed. but it does not occur in coronary and cerebral vascular bed because to ensure maintained blood flow to heart and brain ). * On Hemorrhage  HR . TPR   BP return to normal BP. PULMONARY CIRCULATION : Is 100% of cardiac out put. dilates vessel and increase blood flow. Arterio venous O2 difference  ( due to increase O2 consumption). TPR  (due to vasodilatation of skeletal m bed). ---------------------------------------------------------------------------------- * Blip is aortic P tracing occur following closure of aortic valve also called dicrotic notch or Incisura. 27 . * Symp neurotransmitter is norEN in effector organ except in sweat glands where it is ACh and receptors are muscarinic. * Preganglionic parasymp fibers are long and synapse in autonomic ganglion in effector organ it cell bodies are present in CNS & postganglionic parasym fibers are short & synapse on effector organ. * At rest symp control of blood flow predominate where as during exersize local metabolites control over rides sympathetic control. ( Remember vaso constriction occur in skeletal. unstressed vol  (stress vol ). Pulse P  (due to  stroke vol).KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. contractility . TPR . EN & norEN . its cell bodies are present in autonomic ganglion. * Rapid flow of blood from atria to ventricle cause 3rd heart sound (normal in children but associated with dis in adults). active and reactive hyperemia. stroke vol . * On Exercising  HR . AT II . Local metabolites are most imp mechanism. CEREBRAL CIRCULATION : Is 15 % of resting cardiac out put. cardiac output . * Vasoactive subs in general circulation have little or no effect on cerebral circulation because of BBB. Aldosterone . RENAL CIRCULATION : Is 25% of resting cardiac out put. (because remember preganglionic fibers normally synapse on ganglion). K+.

Beta ( Touch & Pressure) II Sec Afferent of muscle spindle touch & pressure A . bronchial and GI smooth muscles  Relaxation (via cAMP mach) and is more sensitive to EN than norEN and more sensitive to EN than  receptors. STEP IN SENSORY TRANSDUCTION : Stimulus arrives in sensory receptors  opening of ion channel in sensory receptor  inward current cause depolarization ( except in photo receptors where light cause hyper polarization). muscle spindle.* Pacinian Corpuscles (encode vibration and tapping) & adopt rapidly * Meissners corpuscles present on non hairy skin (encode velocity) & adopt rapidly * Merkels disc ( location ) & adopt slowly * Ruffini. 3. light touch respond fast but show decline in action potential frequency with time in response to constant stimulus. pain) III Touch. (note: in vascular smooth muscle M receptors cause relaxation or vasodilation) --------------------------------------------------------------------------------------SENSORY SYSTEM : A. 2. pressure. Type of sensory transducer : 1.Noci Receptors. 2. pacinian corpuscles. IRFAN MIR MD. 3. Muscuranic receptors located on * In Heart M2 receptors are located on SA node  Inhibition (via cAMP) by  the rate of spontaneous depolarization. and lipolysis in fat cells. where as 1 --. contract bladder wall & relax sphincter. (Pacinian vibrates meissners run (velocity) to merkel location and shares ruffini's pressure) B. ADRENERGIC RECEPTOR TYPES : 1.  1 . platelets and fat cells  Inhibition (via cAMP mach). * 1 --. * When small amount of EN release from adrenal medulla cause vasodilation but when large amount of EN release from adrenal medulla for eg as in pheochromocytoma results into vasoconstriction (via  receptors). Temp & Fast Pain B Preganglionic Autonomic Fiber C Slow Pain.s corpuscles (encode pressure) & adopt slowly * Joints.Olfactory Receptors. Trimethpphan ) block nicotinic receptor for Ach in autonomic ganglia but not at neuromuscular junction (because receptors are not identical). * In sweat gland sympathetic action   sweating but neurotransmitter is ACh and receptors are muscarinic. Slow adopting receptor eg. kidney and fat cells  Excitation (via cAMP mach). temp.constrict pupil.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. stretch receptors in muscles * Hair cell in auditory and vestibular system. Presynaptic nerve terminal. 28 . * In Glands  Exitation (via IP3) * In Smooth muscle  Excitation (via IP3) with resultant constriction of bronchial smooth muscle. taste receptors. Pressure.Gamma ( motoneuron to muscle spindle) Intrafusal fiber A .Alpha (large  motoneuron) Extrafusal fiber Sensory Fiber Type Diameter Largest Largest Medium Medium Small Small Smallest Conduction Velocity Fastest Fastest Medium Medium Medium Medium Slowest --------------------------------------------------------------------------------------------------------------------------------------------------------------------------I a (muscle spindle afferent) I b (golgi tendon organ) A . Rapidly adopting receptor eg.located on smooth muscles.  renin secretion. 4.Delta (touch. Photo Receptors ------------. CHOLINERGIC RECEPTOR TYPE : 1. Fiber type and velocity : --------------------------------------------------------------------------------------------------------------------------------------------------------------------------General Fiber Type A . 2.  GI motility and relax sphincter.located on smooth muscle except bronchial smooth muscle  Excitation (via IP3 mech) & is equally sensitive to EN & norEN. pressure.located in heart.heart contraction. Temp (unmyelinated) -------------------------------------------------------------------------------------------------------------------------------------------------------------------------* Receptive Field in the region that contain sensory transducer can be excitatory or inhibitory. 2 . ADOPTATION OF SENSORY RECEPTOR : 1. Ganglion blockers ( Hexamethonium. Postganglionic Autonomic Fiber IV Pain. Chemo Receptors ----------.Rods and Cones of the retina. Respond relatively to prolong stimulus. 4. osmo receptors and Carotid body Receptors. 1 . 2. * Action potential is fired only when stimulus to receptor potential is large enough to exceed threshold. slow pain.  2 .located on vascular. Mechano Receptors -. Nicotnic receptors (activated by ACh or Nicotine) are located in autonomic ganglia & neuromuscular junction  Excitation ( nicotinic or Ach receptors are ion channel for Na+ and K+ ). Temp & Pain Receptors ---.

PAIN: * Perceive by Noci receptors which are free nerve ending and neurotransmitter is Substance P (opiate inhibit it). vibration. (because many rods can activate single bipolar cell).Nearsightedness -. Receive information from primary afferent neuron & send it to thalamus. and movement. neuron sensory project across the midline to the Anterolateral quadrant & ascend to the contra lateral thalamus. * Many Rods synapse on single bipolar cell which results into less acuity & greater sensitivity .Light focus behind the retina (convex lens). * Fast pain fibers are group III fibers shows rapid onset and offset and is localized. IRFAN MIR MD. it ascend ipsilaterally to the Nuc Gracilis & Cuneatus of (Posterior column sys) medulla from here 2nd order neuron cross the mid line and ascend to the contralateral thalamus. * In FOVEA where acuity is high Cone Bipolar ratio is 1:1 .Located in sensory nucleus of thalamus from here it send information to cerebral cortex. 3rd order neuron --. 29 . 2nd order neuron --.Light focus in front of retina (Biconcave lens). * Fiber from Lateral Geniculate Body form Geniculocalcarine Tract and pass to cortex of Occipital lobe. SENSORY PATHWAY : a. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------FUNCTION RODS CONES ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Sensitivity to light Sensitive to low intensity to light ( Night vision ) Sensitive to high intensity light ( Day vision ) Acuity Low visual acuity ( not present in FOVEA ) High visual Acuity ( Present in FOVEA ) Dark Adaptation Rod adopt later Cones adopt first Color vision NO NO More at peripheral of retina YES YES --------------------------------------------------------------------------------------------------------------------------------------------------------------------------* Cutting the Optic nerve  Blindness of ipsilateral eye. * Cutting the Geniculocalcarine Tract  Homonymous Hemianopsia with Macular sparing. 2. * Axon of the Ganglion form Optic Nerve & Optic Tract terminate in the Lateral Geniculate Body of the thalamus. b.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. burnig. throbbing sensation and is poorly localized. * Receptor cells are Rod and Cones which are not present at Optic disc and create a blind spot. * Slow pain fibers are C.Loss of accomodation of lens with aging.Farsightedness -. * Cutting unilateral temporal lobe radiation  Homonymous Quadrantopia (pie in the sky) * Bilateral visual cortex lesion  Macular sparing. 1st order neuron --. Form here 2nd order * Anterolateral system process sensation of temp and pain.Curvature of lens is not uniform (cylindrical lens).Located in spinal cord & brain stem. * Myopia -. 4th order neuron --. The near point appear more farther from eye (convex lens). * Astigmatism -.Primary afferent neuron receive signals.light focus on retina. * Destruction of thalamic nuclei result in loss of sensation on the contra lateral side of the body. * Horizontal and Amacrine Cell form local circuit with Bipolar Cell. Anterolateral System: * Consist of group III and IV fibers which enter the spinal cord and terminate in the dorsal horn. SOMATOSENSORY CORTEX :. * Dorsal column system process sensation of touch.Normal -. * Cutting the Optic Tract  Homonymous Contralateral Hemianopsia. -----------------------------------------------------------------------------------------VISION : * Refractory power of lens is measured by Diopters. Dorsal Column System: * Consist of group II fiber which run in the Dorsal Root. This map of body is called Homunculus (HAL). * Hyperopia -. c. d. (IV) fibers perceive aching. * Few cones synapse on single Bipolar Cell which further synapse on single Ganglion Cell  this arrangement cause high acuity & low sensitivity.Located in cortex and result in conscious perception of stimulus. 10 Diopters = 10 cm * Emmetropia -. S I have somatotropic representation similar to thalamus.* Major somatosensory area of cortex is S I and S II. * Cutting the Optic chiasm  Hetronymous Bitemporal Hemianopsia. -------------------------------------------------------------------------------------------PATHWAY OF SOMATOSENSORY SYSTEM : 1. These cell bodies are located in dorsal root ganglia and CN ganglia. * Presbyopia -. pressure.

Vit A deficiency cause night blindness. Fig: * Middle ear is air filled where as inner ear is fluid filled. 30 . 1. RECEPTIVE FIELD OF VISUAL CORTEX : Detects shape and orientation of figure.Surround ON . * Middle ear contain Tympanic mem. Scala Tympani --. Hyper Complex Cells --. 2. incus.Contain Perilymph and is  in Na+.Contain endolymph and is  in K+* Fig: ( Scala Media is Bordered by Basilar Mem the site of Organ of Corti ).Respond best to lines with Particular Length and to curve and angles. Inhibitory NT depolarize it in response to light. (On Center Off surround is another possible pattern in which light hits the surround of receptive field & hyperpolarize (inhibit) the ganglion cell) * Lat Geniculate Cell of the Thalamus retained the Center . Receptive visual Field : * Light hit the centre of receptive field & depolarize (excite) the Ganglion cells & constitute On Center Off Surround receptive visual field pattern. Simple Cells (have center -surround On . in turn Ossicle vibrate and pushes the stapes in to the Oval Window ( a mem b/w inner ear and middle ear ) which displaces the fluid in the inner ear. * Excitatory NT hyperpolarize bipolar & horizontal cell in response to light. 3. vestibule) and series of Ducts called Membranous labyrinth which contain endolymph (inside the duct) and perilymph (out side the duct). 3. stapes) and Oval window where as Inner ear consist of Bony labyrinth (semicircular canal. * Sound cause Tympanic mem to vibrate.Respond best to moving Bars and edge of light. 2. Scala Vestibuli --. -------------------------------------------------------------------------------------------------------------------AUDITON : * Frequency measure in Hertz where as Intensity in Decibles. * Sound energy is amplified by lever action of Ossicles and send conc of sound wave from Tympanic mem to Oval Window. IRFAN MIR MD. Photo Reception of Rods: * In Rod Photosensitive element is Rhodopsin composed of Scotopsin & Retinine ( Aldehyde of vit A ) .Respond to Bars of light with correct position & Orientation.Contain perilymph and is  in Na+.Off pattern & are elongated Rods) --. Scala Media --. Complex Cells --. COCHLEA consist of three Tubular canals.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. * Light on retina convert 11-cis Rodopsin  All transRodopsin  MetaRodopsin II (active form)  than Metarodopsin II activates G protein called Transducin which in turn activate Phosphodiesterase  Phosphodiestrase further catalyze conversion of cGMP into 5‘ GMP (c GMP level ) . 1. Visual Cortex comprise of three Layers. cochlea. (because Vit A is essential for regeneration of Rhodopsin). Than  cGMP results into closure of Na+ channel & Hyperpolarization of the cell Membrane .OFF pattern transmitted from Ganglion cell. Ossicles (malleus. vs. (  light cause  degree of hyperpolarization ).

* Remember always Medial geniculate to Ear and lateral geniculate to Eye. * During initial counterclockwise rotation Left Horizontal canal is excited & Right Horizontal canal is inhibited but after few seconds endolymph catches up the movement of head & capula. the Axon of olfactory nerve is unmyelinated C fiber and are smallest therefore slowest.Occur in the opposite direction of head Rotation. * Sound wave vibrates Organ of Corti  Basilar mem to vibrate & push against Tectorial mem  Hair cells to bend  bending of cilia (which cause change in K+ conductance)  Depolarization  Ossillating potential results. Saccule --. Utricle --. * Olfactory epithelium is also innervated by trigeminal nerve V which detect Noxious stimulus such as Amonia.Detect angular acceleration and rotation. * Spiral Ganglion contain cell bodies of CN VIII which synapse on Hair cells.Occular Reflex : Nystagmus --. * Olfactory nerve passes through the Cribriform plate to Olfactory bulb. * CN I carries information from receptor cell to Olfactory bulb. 1. 2.Also detect Linear acceleration . IRFAN MIR MD. * Ability to recognize a patterned sequence is a property of Cerebral Cortex. * Cilia protrudes from Hair cells and imbedded into Tectorial mem . * Vestibular . ORGAN OF CORTI is located on Basilar mem.( CN V response is intact ) * Mitral cells in the Olfactory bulb are 2nd order neurons from Olfactory Tract and project to Prepiriform Cortex. (nystagmus in rest arise from disruption in central or peripheral vesticular connection) Post rotatory nystagmus --. in nervous system that turn over and replace neuron. Anosmia. * Odorant molecules bind to the olfactory receptor neuron  activate G protein  activates adenylate cyclase   cAMP  Open Na+ channel  depolarization of receptor potential  Fire action potential. (bending in other direction cause hyperpolarization) * Ossillating Potential (Cochlear microphonic potential) of Hair cell  intermittent firing of Choclear nerve.Detect linear acceleration. * Kinocilium is a single long cilium where as Stereocilia are small cilium.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. its fracture  Hypoosmia. it will now hyperpolarized and hyperpolarized one will depolarize. It conduct action potential to CNS via CN I.(no more hyperpolarization or depolarization) * When head suddenly stops endolymph continues to move to counterclockwise for a while (cause cilia to move in opp direction)  if the hair cell was depolarized with initial movement. ENCODING OF SOUND WAVE : * Base of the Basilar mem ( near Oval and Round window ) is narrow and stiff it respond best to high Frequency. 3. * These neuron are the only eg. ----------------------------------------------------------------------------OLFACTORY receptor cells are present on epithelia and are true neurons. * Apex of the Basilar mem ( near Helicotrema ) is wide and compliant it respond best to low Frequency. * Vestibular Hair cells are embedded in gelatinous substance called Capula. * If Sterocilium bends toward the Kinocilium  Hair cells Depolarize where as If Sterocilium bends away from Kinocilium  Hair cells Hyperpolarize. * Fiber may crossed or uncrossed that’s why lesion of the chochlea of one ear cause unilateral deafness where as more central unilateral lesion does not cause complete unilateral deafness.An initial rotation of head cause eye to move slowly in opposite direction when limit of eye movement reaches the eye rapidly snap back than move slowly again. * The vestibular receptor cells are Hair cells located at the end of each semicircular canal. Its Receptors are inner Hair cells (in single row) & outer Hair cells (in parallel row) Outer Hair cells are greater in number than inner Hair cells. VESTIBULAR SYSTEM : * Vestibular organ is a membranous labyrinth consisting of three perpandicular canal filled with Endolymph. cilia return to their upright position. CENTRAL AUDITORY PATHWAY : * Cochlear nerve Fiber ascend through Lateral Laminiscus  Inferior Colliculus  Middle Geniculate nucleus of thalamus  auditory Cortex. Semicircular canal --. 31 .

* Stretched muscle further stretches Muscle spindle  Stimulate a (velocity) & group  (static) afferent fibers  stimulate  motoneuron in spinalcord  contraction. (single motoneuron may innervate few muscle for fine movement & many muscle for large movement) . 2. * CN VII.Finer movement need greater no of muscle spindle in muscle. Muscle spindle a has parallel arrangement with extrafusal muscle fiber.innervate many muscle fibers. * Small motoneuron -. from here itproject primarily ipsilaterally to ventral posteromedial nuc of thalamus  taste cortex (which is present in the ventral region of Post central gyrus).innervate few muscle fibers. 4.are smaller than extrafusal fiber. TYPE OF MUSCLE FIBER :1.  &  motoneuron are coactivated so muscle spindle remain sensitive to change in muscle length during contraction. Intrafusal fiber -. . FUNCTION OF MUSCLE SPINDLE : Muscle spindle opposes over stretching of muscle by contracting it. Function of  Motoneuron :. 3. * Back of throat and Epiglottis is innervated by vagus nerve X. has lower threshold therefore fire first and generate small force. * Motoneuron pool is a group of neuron that innervates fibers with in same muscle. Intrafusal Fiber  a type afferent  muscle strength (dynamic changes)  Nuc bag fiber Nuc chain fiber  muscle change (static change)   type afferent ------------------------------------------------------------------------* Muscle spindle -. X enter the medulla ascend in solitary tract where 2nd order neuron terminates in solitary nucleus. It encapsulated to form muscle spindle & run parallel to extrafusal fiber but do not run entire muscle length. 2.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr. 1. * Large motoneuron -. has highest threshold and therefore fire last and generate large force. V detect noxious stimuli. It provide force of muscle contraction.4 Types of muscle sensors 1. ( taste receptors are present on taste bud ) * Ant 2/3 of tongue has Fungiform Papillae  detect salty and sweety sensation and is innervated by Facial nerve VII. MUSCLE REFLEXES --------------------------------------------------------------------------------------------------------------------------------------------------------------------------REFLEX NO OF SYNAPSE STIMULUS AFFERENT FIBER RESPONSE ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Stretch Reflex ( Knee Jerk ) Monosynsptic Stretch Muscles a Muscle contraction Golgi Tendon Reflex ( Clasp Knife ) Disynaptic Contract muscle b Muscle Relaxation Flexion withdrawal Reflex Polysynaptic Pain . IRFAN MIR MD. * Post 1/3 has Circum vallate & Folliate papillae  detect sour & bitter sensation & is innervated by Glossopharyngeal nerve IX. Golgi tendon organ b has serial arrangement with extrafusal muscle fiber detect muscle tension. TASTE : * Taste buds are located on special Papillae & are covered with micro villi. Nuclear Bag fiber: Detect Dynamic changes (rate & change in muscle strength at motion) & is Innervated by a afferent.make muscle bulk and stimulate by  motoneuron. * Force muscle contraction is graded by recruitment of additional motor unit (size principle). (muscle spindle consist of intra & extra fusal muscle fiber) * There are two type of intrafusal fiber present in muscle spindle. 2. ------------------------------------------------------------------------MUSCLE SENSORS :. V Ipsilateral Flexion & contralateral ( after touching Hot object ) Extension ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 32 . IX. Nuclear Chain fiber: Detect Static change (at rest) in the muscle length & is innervated by group  afferent. -------------------------------------------------------------------------MOTOR SYSTEM :* Motor unit is a single motoneuron plus muscle fiber that it innervates. Pacinian Corpuscles  detect vibration. Motoneuron Innervate intrafusal muscle fiber it adjust the sensitivity of muscle spindle. Extrafusal fiber -. Free nerve ending . detect both static & dynamic changes in muscle length.

Both Pass through medullary pyramids. It stimulate flexors & inhibit extensor. Lateral Vestibulospinal Tract -. 3. Flexion withdrawal reflex -. as in hanging. Paraplegia (Loss of voluntary movement) below the level of lesion.(but more Ext) 4. Convergence is when more than one muscle spindle stimulates single motoneuron ( a afferent ) produce spatial Summation ( more than one input bring muscle to threshold ) & temporal summation ( input arrive rapid succession ).remove inhibition from higher center and cause excitation of  and  Motoneuron  Decerebrate rigidity (rigid posture).Originate in nuc in pons & project to Ventromedial spinalcord. FUNCTIONS --. After discharge does not allow the muscle to relax for some time because of persistent neuronal activity in polysynaptic circuit. Stretch Reflex -. * Lesion above Pontine Reticular formation -. 2. Tactospinal Tract -. 3. 2.After touching a hot object pain stimulus from . Initial loss of reflexes (spinal shock) flaccidity occur below the level of lesion due to loss of  &  motoneuron.Central control of movement. 1. Divergence is when a afferent (muscle spindle) project to more than one or all motoneuron of the homonymous mus.Originate in red nuc & project interneuron to lateral spinalcord. Rubro spinal Tract -.Originate in superior colliculus & project to cervical spinal cord. Clasp Knife reflex is an exaggerated form of the Golgi tendon ref it can occur in Corticospinal tract dis → ( spasticity ). Synergy (Control of rate. Loss of conscious sensation below the level of lesion.1. Recurrent inhibition (Renshaw cells): Renshaw cells are inhibitory neuron it inhibit motoneuron (. 2.a afferent synapse on  motoneuron to cause contraction in the muscle that was stretched. It receives input from collateral axons of motoneuron. Control of Balance an eye movement conduct by Vestibulo Cerebellum. ----------------------------------------------------------------------CEREBELLUM :.is Corticospinal & Corticobulbar Tract. --------------------------------------------------------------BRAIN STEM CONTROL OF POSTURE : Motor center and Pathway are of two types. 3.ve feed back ) in ventral horn of spinalcord.removal of inhibition from pontine reticular formation & resultant excitation of  &  motoneuron & cause Decerebrate rigidity (rigid posture) * Lesion above the Red Nucleus  results in Decorticate Posturing and intact tonic neck reflex. IRFAN MIR MD. Force. It stimulate extensors & inhibit flexors.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr.(but more ext) 5. Medullary reticulospinal Tract -. It stimulate both extensors & flexors.Originate in Dieter’s nuc & project to Ipsilateral motoneuron & interneuron. Pontine Reticulospinal Tract -. ( with time partial recovery and return of reflexes or even hyperreflexia will occur ) * C7 lesion results into loss of sympathetic tone to the heart   HR &  BP . It control neck muscles. 33 . --------------------------------------------------------------SPINAL ORGANIZATION OF MOTOR SYSTEM : 1. Pyramidal Tract -. Golgi tendon Reflex -. * C3 lesion will stops breathing because respiratory muscle disconnected from brain stem Control center.are all other pathway. EFFECT OF TRANSECTION OF SPINAL CORD : 1. Planning and Iniciation of movement control by Ponto Cerebellum. and V afferent fiber cause ipsilateral Flexion and contralateral extension ( cross extension reflex ) to maintain balance. . 2. (   motor activity   the sensitivity of muscle spindle which result into exaggerated stretch reflex ). Range and Direction of movement) control by Spino Cerebellum. Extrapyramidal Tract -. -------------------------------------------------EXTRAPYRAMIDAL TRACTS AND ITS ORIGINS : 1. 2. 3. * C1 lesion cause Sudden death eg.Originate in medullary Reticular formation & project to spinalcord. It inhibit both extensor & flexor.Activated muscle contraction stimulate b afferent fiber of Golgi tendon  than b inhibit interneuron in spinal cord which further inhibit  motoneuron  Relaxation of muscle that was originally contracted. EFFECT OF TRANSECTION ABOVE THE SPINAL CORD : * Lesion above Lateral Vestibular Nucleus -.

Dendrites of perkinji & golgi type II cells & parallel fibers (axons of granule cells). Mossy fiber give rise to parallel fiber  excite multiple perkinji cells as well as inhibitory neuron  inhibition. Premotor Cortex & Supplementary Motor Cortex ( area 6 ) generate a plan for movement . Straitum Lesion  Quick continuous uncontrollable movement as in Huntington.Play role in cerebral motor learning.KICK THE BOARDS “USMLE STEP 1” Layers of cerebellar cortex : Prepared by Dr.inability to stop movement. It originate in inferior Olive (medulla) make multiple synapse on perkinji cells results in complex Spikes. Disorder of Cerebellum ( Ataxia ) : Lack of coordination: (Poor execution & delayed inhibition of movement). Many of its synaptic connection are inhibitory and use GABA. 2. EEG Findings : * EEG wave consist of alternating excitatory & inhibitory synaptic potential in the pyramidal cell of the cerebral cortex. 1. Out put of cerebellar cortex : * The only out put from cerebellar cortex are perkinji cells and is always inhibitory (neurotransmitter is GABA) * Inhibitory out put project to deep cerebellar nuclei and vestibular nuclei. Substantia Negra Lesion  Destruction of Dopaminergic neuron  Over reactivity of inhibitory pathway of Straitum & Globus pallidus  Lead pipe rigidity. In alert adult  waves predominate & Upon relaxation  waves predominate where as during sleep slow waves predominate.Control of movement * Basal ganglia plan and execute smooth movement by modulating thalamic out flow to motor cortex. It synapse on perkinji fibers (via interneuron) & on glomerular Complex. 2. (caused by release of inhibition) 4. Inability to perform rapid alternating movement called Dysdiadochokinesia. Putamen Lesion  involuntary purposeless muscular movement called Chorea. Granular Layer ( inner most ) -. resting tremor & reduced voluntary movement (Parkinson Dis). Sub Thalamic Nucleus Lesion  Wild flinging movement called Hemiballismus. IRFAN MIR MD. Connection of Cerebellar Cortex : * Input of cerebellar cortex : 1. 5. (caused by release of inhibition on contralateral side) 3. Golgi II cells & Glomeruli. Climbing Fibers . Intension tremer occur during voluntary movement. 3. Rebound Phenomenon . ( In glomeruli axons of mossy fibers form synapse on granular & golgi II cells ). * EEG change occur due to cortical evoked potential. * It is active during Mental Rehearsal for movement which than transfer to primary motor cortex for execution. 2. * Homunculus is upside down Representation of the Human Body in cerebral cortex. (Its lesion results into loss of GABA) Basal Ganglia consist of :1.contain Stellate & Basket cells. Mossy Fibers . -------------------------------------------------------------------------- HIGHER FUNCTION OF CEREBRAL CORTEX :1. Perkinji Cell Layer ( middle layer ) -. * Epileptic event in Primary motor cortex  Jacksonian Siezures. -----------------------------------------------------------------------BASAL GANGLIA :. 34 .Originate in brain stem & spinalcord. MOTOR CORTEX :1. It regulates synergy. Globus pallidus Lesion  Inability to maintain postural support and athetosis (involuntary slow movement of hand & foot).contain granule cells.out put is always inhibitory. Molecular Layer ( outer layer ) -. Primary Motor Cortex ( area 4 ) is responsible for execution of movement. 2.

* Protein and cholesterol are excluded from CSF because of large molecule size. SLEEP : * Sleep wake cycle occur in circadian rhythm which resides in Suprachiasmatic nucleus of hypothalamus. * Composition of CSF is same as interstitial cerebral fluid of brain. Short Term Memory: Involve synaptic changes. * Damage to Wernicks Area  Sensory Aphasia ( difficult to understand written and spoken language ) . FUNCTION : * BBB maintain constant enviornment of neuron in CNS and prevent scape of CSF and neurotransmitter. 35 . * Heat can also loss by evaporation via sweat glands activity which is under sympathetic muscuranic control. * Non Ionized ( lipid soluble ) drug absorb more easily than ionized ( non lipid soluble ). * Damage to Broca Area  Motor Aphasia ( In which speech and writing are affected but understanding is intact ). 5. Its lesion  Aphasia. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- TEMP REGULATION : * Thyroid hormone   metabolic rate  heat production ( by stimulating Na+ . 4. or tumor cell may destroy BBB. IRFAN MIR MD. * Inflamation. Radiation. * Cold Temp  Activate sympathetic sys  metabolic rate & heat production (via  receptors activation on brown fat) * Shivering is most potent heat generating response by Post Hypothalamus ( via  &  moto neuron  contractions ). Intonation (voice tone). COMPOSITION OF CSF & BLOOD CONC : --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------CSF  BLOOD CSF  BLOOD CSF  BLOOD --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Na+ K+ Mg++ ClCa++ Creatinin HCO3Glucose Osmolarity Cholesterol & protein. LANGUAGE :* Left hemisphere is usually dminant with respect to language even in left handed person. and Spatial task. * If core temp is below or above normal it activate SET . Body language. 2. O2. HYPOTHALAMUS SET. During REM sleep EEG resembles that of awake person. ( bilateral hippocampus lesion  no more new long-term memories) ---------------------------------------------------------------------BBB AND CSF : * BBB consist of endothelial cells of cerebral capillaries and choroids plexus epithelium. * Right hemisphere is more dominant in Facial expression. * Cold and Pyogens ( inflammatory products and mediators )  the SET . * Rapid eye movement sleep occur every 90 min.POINT temp. HEAT LOSS : * Heat loss response is also control by Post Hypothalamus. 3.POINT heat generating or losing mechanism via Post hypothalamus. *  Temp   sympathetic tone to the skin and blood vessels  shunting the warm blood near the surface of the skin   heat loss by radiation and convection. Long Term Memory: Involve structural changes & is resistant. & H2O cross BBB freely but other subs transport (in & out) by carrier in choroid plexus epithelium.POINT FOR BODY TEMP : * Temp sensors on the skin and hypothalamus read the core temp and relay information to ant hypothalamus which compare core temp with SET .POINT temp. Most dream occur during REM sleep. * Slow wave sleep is Dream less Sleep ( dream do occur but cant be remmember ). which receives input from retina.K+ ATPase ).  age and Benzodiazepine   in REM sleep. * Lipid soluble subs like CO2.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr.

* 1 -. * Protein produce by platelets is thromboplastin. * Parasympathetics contract smooth muscle but relax sphincter by muscarinic receptors. IRFAN MIR MD.In heart cause contraction where as in kidney cause Renin release. vs. * In carotid sinus Baro receptors respond strong to rising Pressure than falling pressure. * 2 -. * Heat stork: occur when body temp  to the point of tissue damage due to impaired sweating response   core temp. ---------------------------------------------------------------------Few Points * Renshaw cells (neuron) respond to Ach and receptor is nicotinic. Parkinson dis cause resting tremor.KICK THE BOARDS “USMLE STEP 1” Prepared by Dr.In Adipose tissue  lipolysis. exception in eye where  receptors contract radial muscle and cause mydriasis. FEVER : Pyogens produce IL-1 which act on ant hypothalamus to  the production of prostaglandins which  the SET – POINT temp and generate heat (fever). HEAT EXHAUSTION AND HEAT STORK : * Heat exhaustion: is caused by excessive sweating   Blood vol   BP  Syncope . * Cerebellar lesion cause intention tremor (tremor during voluntary movement). It is characterized by  in O2 consumption and heat production by skeletal muscle  rapid  in body temp. Imp difference * Difference b/w decerebrate and decortical rigidity and other signs ? 36 . * Malignant hyperthermia: caused by inhalation anesthetics in susceptible individual. * Sympathetics relax smooth muscle and contract sphincters by  receptors.Relax smooth muscle * 3 -. * Hypothermia: results when temp is low and shivering & metabolism can not adequately maintain core temp near SET POINT.

Sign up to vote on this title
UsefulNot useful

Master Your Semester with Scribd & The New York Times

Special offer for students: Only $4.99/month.

Master Your Semester with a Special Offer from Scribd & The New York Times

Cancel anytime.