End of Exam 1 material Flashcards
Peritoneum
the membranous lining of the abdomen (heart is pericardium and lungs is pleura) have parietal peritoneum (lining body cavity), visceral peritoneum (lines organs), and mesentery
Mesentery
Greater omentum (connects inferior to stomach to transverse colon; large flap of mesentery draps over rest of GI tract [small intestine] ) and lesser omentum (connects liver to stomach; site of omental bursa or hole connecting greater and lesser sacs; has hepatogastric ligament, hepatoduodenal ligament, and epiploic foramen(connects the 2 spaces))
Greater sac
anterior to the greater and lesser omentum
Lesser sac
posterior to the greater and lesser omentum
Intraperitoneal
covered in peritoneum, associated with mesentary; ex. stomach, small intestine (jejunum, ileum, some of duodenum) spleen, liver, gallbladder, vermiform appendix, some large intestine, (transverse colon, sigmoid colon) nerves and blood vessels travel though mesentery
Primary retroperitoneal
develops and stays behind (retro) the peritoneum ex. kidney and suprarenal glands
secondary retroperitoneal
originates within but merges back into peritoneum, ex. duodenum (descending, horizontal, ascending), pancreas, colon (ascending and descending) and rectum
Stomach location
sits on the left side of abdomen, roughly 9th rib, level of pyloris ; in the right/left upper quadrant AND right/left lower quadrant (trans-pyloric plane); connects to the liver via the lesser omentum
Stomach function and anatomy
Primarily digestion (proteases), some absorption; cardia (by esophagus), fundus (top of stomach), body (has longitudinal rugal folds), lesser curvature, greater curvature, pylorus (at end; has a pyloric sphincter)
The portal triad
bile duct, portal vein, proper hepatic artery; these 3 travel together through the hepatoduodenal ligament, cover the epiploic foramen
Duodenum
First part of small intestine, runs from right upper quadrant to left upper quadrant; releases bile (lipid digestion), bicarbonate (acid neutralization) and pancreatic enzymes (digestion); 1st part- superior (posterior part of cavity) intraperitoneal; 2nd part- descending (pancreatic glands/bile excreted; has minor duodenal papilla [doesn’t connect with bile] and Ampulla of Vater or the major duodenal papilla which is the major source of where bile is secreted) secondary peritoneal; [roughly site of foregut/midgut transition] ; 3rd part -horizontal (rungs under superior mesenteric artery) secondary peritoneal [passes under the SMA]; 4th part- ascending (rises from a posterior part, forward) intraperitoneal ; has circular folds, papilla, and Brunner’s glands
Jejunum and Ileum
2nd and 3rd parts of the small intestine, site of nutrient absorption; runs left upper quadrant to right lower quadrant; no distinct line separating jejunum and ileum; jejunum connects to the duodenum (Brunner’s glands and circular folds) and has large circular folds; the ileum has peyers patches, and small circular folds and connects to the large intestine (cecum)
large intestine/colon
Absorption, especially water; on right/left upper quadrant and right/left lower quadrants; cecum (base of colon), appendix (lymphoid tissue), ascending colon, right colic flexure (hepatic), transverse colon (drapes down; intraperitoneal), left colic flexure (splenic), descending colon, sigmoid colon (bend before rectum, intraperitoneal), rectum AND ileocecal valve (entry from ileum to colon), tenia coli (longitudinal bands of smooth muscle), haustra (bulges caused by tenia coli), semilumar folds (inside, depression/internal ridge found between haustra), and epiploic appendices (fat)
Liver
Production of bile, hormones, enzymes, filtering of blood, etc. Found in the right upper quadrant , has right and left lobe in the anterior view, has caudate lobe (between IVC and fissure for teres ligament; often receives blood from both left and right hepatic arteries) and quadrate lobe (between gallbladder and teres ligament) which are much smaller lobes in the posterior view; has falciform ligament separating the 2 anterior lobes, and round ligament (ligamentum teres of liver) at the end that is a remnant of the umbilical cord vein [does nothing; going toward the fetal heart from mom]; has a superior surface bare area (where diaphragm sits; parietal and visceral peritoneum fuse into diaphragm and the bare spot is where neither parietal nor visceral pleura is present )
Gall bladder
In the right upper quadrant, Storage and concentration of bile; tucked under right inferior lobe of liver; connects to both lier and ampulla of Vater in the descending part of the duodenum
pancreas
In the left upper quadrant, production of digestive enzymes and bicarbonate, secondary retroperitoneal, surrounded by the entire duodenum
Spleen
In the left upper quadrant; Removes blood cells, immune functions
Kidneys
In the left and right upper quadrant; filters blood, produces urine, primary retroperitoneal; attached to the suprarenal glands that lay on top –> ureter–> urinary bladder
Adrenal glands
In the left and right upper quadrant; lay on top of the kidneys; stress response, sex hormones, metabolism, immune system, etc; primary retroperitoneal
Foregut
From stomach to duodenum; celiac trunk (L1)
Midgut
from 1/3 of duodenum to 2/3 of colon; Superior mesenteric artery (L1)
Hindgut
From descending colon to rectum; Inferior mesenteric artery (L3)
Celiac trunk
(L1) Serves foregut, liver, gallbladder, and spleen; has 3 branches (left gastric [DOES NOT HAVE BRANCHES], splenic, and common hepatic)
Superior mesenteric artery
(L1)Serves midgut (duodenum to transverse colon) branches into Inferior pancreatic duodenal artery, middle colic artery, jejunal and ileal arteries, ileocolic artery, and right colic artery [horizontal/ inferior duodenum travel under the SMA]
Inferior mesenteric artery
(L3) Serves hindgut (descending colon to rectum) branches into left colic artery, sigmoid arteries, and superior rectal artery
Splenic Artery
Branch of Celiac trunk; Goes into spleen and branches into Left Gastro-omental artery and pancreatic branches
Common Hepatic Artery
Branch of Celiac trunk; branches into proper hepatic artery, right gastric artery, and gastroduodenal artery
Gastroduodenal Artery
Branch of Common Hepatic Artery; branches into right gastro-omental artery, Anterior and posterior superior pancreaticoduodenal artery, and duodenal branches
Anastomes within and between foregut
superior pancreaticoduodenum A. AND SMA, or left AND right gastric A. or, left AND right gastroomental A.
Anastomes within and between midgut
marginal artery of drummond (with similar collaterals for veins) or watershed (left colic flexure- risk for ischemia[necrotic tissue, cells can die; left colic and middle colic fuse into)
Anastomes within and between hindgut
middle AND inferior rectal arteries- come from the internal iliac artery
Renal arteries
(L1/L2) supply the kidneys; between SMA and IMA
Iliac arteries
Common iliac(main one that separates into external and internal), external iliac (supplies legs) and internal iliac (supplies rectum, inguinal region); superior to them is the aortic bifurcation (L4)
Veinous drainage of the Gastrointestinal
2 separate paths- caval (systemic) and portal; if it is NOT the GI tract, it is drained by the systemic system (ex. the IVC); If it IS the GI tract, it is drained by the portal system which in turn drains into the IVC; NOTE: the left testicular/ovarian vein drains into the left renal while the right testicular/ovarian vein drains into IVC
Caval systemic system
IVC; right and left inferior phrenic V, right suprarenal V, right and left renal V. (branches into left testicular/ovarian V and left suprarenal which anastomosis with left inferior phrenic), and right testicular/ovarian veins
Caval Portal system
Foregut( the same tissues drain via similarly named veins into the portal vein vs. the celiac artery) , midgut (SMV; the same tissues drain via similarly named veins into the SMV vs the SMA), hindgut (IMV; the same tissues drain via similarly named veins into the IMV vs the IMA)
Key things to remember about the portal system
Blood flows INTO the liver via the portal vein. Blood flows out of the liver by draining into the IVC, back into the systemic circulation
The IMV drains into the splenic V, which then drains into the portal vein
The SMV drains directly into the portal V.
Portal Caval Anastomes
No valves: flow can be in any direction, depending on the pressure gradient; 1. esophagus 2. rectum (anus) 3. superficial abdomen (umbilicus)
Esophagus Portal Caval Anastomoses
Portal (gastric veins to HPV)
Caval (Esophageal veins to Azygos veins)
Ex. blockage in the liver parenchyma (ex. cirrhosis) Forms esophageal varices which are enlarged veins that develop when normal blood flow to the liver is blocked
Rectum Portal Caval Anastomoses
Portal( superior rectal veins to IMV to HPV)
Caval ( Middle and inferior rectal veins to internal iliac vein to common iliac vein to IVC)
Ex. Internal hemorrhoids (swollen veins around anus/ lower rectum) go through the caval route
Superficial Abdomen Portal Anastomoses
Portal (paraumbilical veins to HPV)
Caval (Epigastric veins to femoral vein to external iliac vein to common iliac vein to IVC)
Ex. Caput medusa (superficial veins of abdominal wall) causes flow toward the legs
Portal Hypertension
Gut (esophageal varices), Butt (internal hemorrhoids), Caput (Caput Medusa)
Portal hypertension is an increase in the blood pressure within the portal venous system.
Distal splenorenal shunt (DSRS) is a surgical procedure that connect the splenic and left renal vein (relieves portal hypertension by decreasing blood volume delivered to the liver through bypassing the hepatic portal vein and delivering blood from the splenic vein into the left renal vein)
Metabolic requirements for O2/CO2
O2 is required for aerobic respiration; clearance of CO2 the byproduct of aerobic respiration is also important; the respiratory and circulatory systems are built around the need to move O2 into and through the body while collecting CO2 and expelling it
Diffusion of Gases: Partial pressure
Partial pressure is the pressure of an individual gas in a given volume at a constant temperature (the summative force exerted by the collision of gas molecules at the alveolar surface at any given time); It is not the same as concentration although it is directly proportional to the concentration of a gas (one rises and fall with the other)
Total pressure (atmospheric pressure is 760mm Hg or 1 atm [sea level]) –> divided into 21% (pp O2 160mm Hg) and 79% (pp N2 600mm Hg)
Diffusion of Gases: The ‘Inside/Outside” transition
The alveoli are ventilated with air through inspiration; at the alveolar membrane, gas moves into/out of the circulatory system by diffusion (GAS DIFFUSES INTO A LIQUID into capillary[or out of liquid into alveolus]); ideally, O2 moves into the blood, while CO2 moves out. The respiratory system functions to maintain the partial pressure of O2 and CO2
Alveolar Air vs Atmospheric Air
The air at the alveolar membrane has somewhat different composition than atmospheric air (less O2, more CO2, and is humidified); water vapor at normal body temp. is 47 mm Hg. This is added to the mix of gas in the alveoli as air is drawn through the respiratory passages. It serves to dilute the other gases (NOT LESS, JUST MORE DILUTE)
Diffusion of Air into Blood
An essential step in this process is the movement of gas molecules across a membrane and into a liquid suspension; Different gases have different levels of attraction to water molecules (blood) and will therefore have different levels of solubility in water (ex. CO2 is highly soluble in blood, O2 is much less so); The NET direction of diffusion relates directly to relative partial pressure of gas on either side of the membrane so RATE of diffusion in the net direction will be affected by:
- Solubility of the gas in the fluid
- Surface area of the barrier across which diffusion occurs
- Distance of diffusion (membrane thickness)
- Molecular weight of gas
- Temperature (not usually an issue because always at 37C)
RESPIRATORY GASES ARE HIGHLY SOLUBLE IN LIPIDS cells/tissues), THUS AQUEOUS DIFFUSION IS THE LIMITING FACTOR
Diffusion of O2 into Blood
Respiration is all about maintaining the partial pressure in each space; This system can be modified in situations of high metabolic stress
Rate of diffusion= (ΔPAS)/(d*sqrt(MW))
Increased ventilation/blood flow= increased ΔP (pressure difference or gradient)
vasodilation/increase ventilation= increase A (surface area)
Solubility constant= increased RBC
Distance of diffusion can be PATHOLOGICALLY increased
Functional Residual Capacity
Not all of the air in lungs is expelled with each breath; Around 2300mL (70kg male) of air remains in lungs, with 350 mL being exchanged with each breath during ‘normal’ respiration; The exchanged volume is known as tidal volume (normal volume of air displaced between inhalation and exhalation); Functional residual capacity acts as a buffer that prevents sudden changes in the alveolar gas mix, which is useful for keeping blood gas levels relatively constant (maintains diffusion); This greatly enhances the stability of the lungs as a regulatory mechanism for O2, CO2, and pH
O2 content of the Alveoli
Amount of O2 in alveoli at a given time is controlled by: 1. Ventilation from breathing 2. rate of absorption from the blood
This is a dynamic system, linked with metabolism: Increase in metabolic demand, decrease to amount of O2 in the blood
Decrease in the pp of blood O2 increases diffusion from the alveoli, resulting in a decreased O2 pp in the lung, which is counterbalanced by increased ventilation and pulmonary blood flow
CO2 content in the alveoli
Inverse of O2; increased metabolic load (in tissues) leads to an increase in blood CO2 (and decrease in pH) which in turn increases exchange of CO2 into the alveolus; This excess CO2 is removed by increasing ventilation and pulmonary blood flow [brain very sensitive to CO2 levels]
The ventilation/perfusion ration
The relationship between alveolar ventilation and alveolar perfusion; Pathologically, an individual may have good air flow to a group of alveoli, but poor perfusion (blood). Inverse is also true; The ratio between VA (ventilation of a given alveolus) and Q, the blood flow to that alveolus= VA/Q which can be expressed as a function of pp of O2 and CO2 in an alveolus:
At VA/Q=0, we have no air reaching the alveolus, thus 0/Q=0. PP of both gases in the alveolus equilibrate with that of the pulmonary blood [all perfusion, no ventilation]
At the other end of the scale, if no blood perfuses an alveolus, Va/0= infinity. No gas exchange happens thus the pp of O2 is equal to humidified air, while no CO2 is exchanged.
In both situations, no actual respiration is taking place.
The physiological shunt (when VA/Q–> 0)
We know from experience that one can outstrip the capacity of the lungs to supply O2 to the blood in the amounts required (non-aerobic exercise). Some blood sent to the lungs also perfuses the bronchioles and is not oxygenated. This can also be the case in various respiratory disease.
This non-perfused blood is called SHUNTED BLOOD, and the amount that passes through the pulmonary circulation/min is called the PHYSIOLOGICAL SHUNT. When VA/Q ratio is lower than normal (supply is not sufficient to oxygenate all perfusion) you have SHUNTED BLOOD.
QPS/QT= Ci02- Ca02/Ci02-Cv02 QPS= shunted blood flow/min QT= cardiac output/min C(iO2)= theoretical [O2] at ideal VA/Q Ca(O2)= measured arterial O2 Cv(O2)= measured venous O2
Physiological Dead Space
Not all inspired air is available for gas exchange because some of it remains in the respiratory passages or arrives in alveoli that are not particularly perfused with blood (especially at rest). This volume is called the PHYSIOLOGICAL DEAD SPACE AIR (there but can’t do much) VA/Q is greater than normal (goes toward inf) as supplied ventilation is greater than perfusion.
VDPhys /VT= PaCO2-PECO2/ PaCO2
VDPhys= Physiologic dead space (Bohr equation) VT= Tidal Volume PaC02= Pp of arterial CO2 PEC02= Mean Pp of CO2 in expired air
Normal Alterations to VA/Q
In a standing person, blood flow is somewhat less in the top of the lungs than in the bottom. VA/Q is ~2.5x HIGHER than normal (in upper part of lung) giving physiological dead space.
In the lower portion of the lungs, blood flow is much greater, and relative ventilation slightly insufficient. This VA/Q is 0.6x the ideal, giving a normal physiological shunt in this region (approaching more blood than air)
Exercise minimizes these, especially the physiological dead space, due to increased perfusion.
Ventilation is also lower in the upper part of the lung, but as we are talking about relative proportions of each dead space exists, while a shunt exists in the lower part.
Pathological Alterations to VA/Q
Obstructed lung disease (ex. emphysema and other effects of smoking) cause all sorts of problems in the lungs. They can cause both obstruction of certain bronchioles (and this attendant alveoli) to be poorly or non- ventilated. Also distance of diffusion across damaged alveolar membranes can be increased. Both result in shunted blood.
Alveolar walls and vasculature can be damaged, resulting in decreased perfusion, even when the ventilation is sufficient, resulting in increased dead space.
This in obstructive lungs disease, there is a mixed situation with some parts of the lung shunting blood and in other parts increased dead space. The summative effect of both of these results in a significantly decreased respiratory efficiency.
Transport of Blood Gases
(CO2/O2 into and out of blood)
Transport of both depend on:
1. Their rate of diffusion into and out of the blood 2. Movement of blood (how much passes a given point per time) [ how much can you get in/out over time and how quickly can you move it about the body]
DO2= CO x CaO2
DO2= Delivery of O2 to tissues CO= Cardiac Output (how much heart is pumping over time) CaO2= Arterial Oxygen Content
Transport of O2 in the blood
blood leaves alveoli with a pp of O2 around 104mm Hg. After mixing with shunted blood from bronchioles/ deep tissues it is around 95 mm Hg, the average arterial pp of O2. As the arterial supply diverges into capillaries, O2 diffuses out, bringing the pp of O2 back to around 40 mm Hg or the average venous pp. As we increase blood flow, we can increase O2 delivery, but pp is capped at ~95mm Hg. In the tissues, O2 pp is greatly decreased by diffusion and encounters individual cells at around 23 mm Hg. okay because Intracellularly only 1-3 mm Hg are generally required to support cell process.
Problem with transporting O2 in blood is that its not very soluble in blood. RBC have hemoglobin (hb) which can loosely and reversibly bind O2 making it much more soluble. Around 97% of all O2 transported by the blood is bound to hb (rest is freely dissolved).
Hemoglobin- O2 dissociation
High pp of O2 favor hb binding of O2, while low pp of O2 favor the disassociation of O2. So when plenty of O2 (pulmonary circulation) it tends to load, but when one needs O2, it’s unloaded and diffuses into tissue.
The total content of O2 in the arteries is therefore dependent on the pp of free O2, the amount of hb, and how much hb is carrying
CaO2= (1.34 x [hb] x SaO2) + (.003 x PaO2)
CaO2= Arterial Oxygen Content( amount of O2 that can be carried) [hb]= Concentration of hemoglobin (by pumping out more RBCs) SaO2= O2 saturation of hemoglobin PaO2= Arterial partial pressure of O2 (pressure of O2 not bound)
CO2 is the inverse of this
Hemoglobin binding of O2
Hb has 4 sites which are capable of binding O2; O2 is bound to hb as elemental (diatomic) O2, not ionic so for each binding site you get 2 O atoms. These 4 sites demonstrate COOPERATIVE BINDING. For each site occupied, the affinity of the following site for O2 is increased, meaning it more easily binds O2. (greater O2= more affinity for hb binding of O2) increasing Hb (more RBCs) or increasing saturation of Hb is far more powerful than just increasing the pp of O2 in blood
Each RBC has many hb molecules. Saturated RBCs will hold onto their O2 with great affinity because of cooperative binding. When faced with low peripheral blood or tissue O2 levels, the first of 4 bound molecules O2 will dissociate and with each O2 that disassociates, the easier it is for the following molecules [reverse of CP]. The lower the O2 level, the more inclined hb is to unload (ex. in tissues). The % of blood that gives up its O2 is called the utilization coefficient (conditions in tissue using little O2) and is, at rest around 25%. In exercise, this increases to ~85%.
In tissues have lowered pp of O2, lowers further when doing work
O2 Disassociation curve
The relationship between hb saturation and pp of O2 forms a sigmoid curve. As the pp of O2 exposed to hb increases, so does the saturation of the hb. The sigmoidal shape shows the diminishing returns of adding more O2 when hb approaches total saturation.. The steeper section of the curve reflects the cooperative binding of O2 and hb. [hb acts as a buffer to resist change in tissue PO2
Shifting the O2 Disassociation Curve
Conditions in the blood can alter the affinity of hb for O2. Physiologically we want areas undergoing high metabolism to favor the release of O2 (decreased affinity), while we want well ventilated conditions to favor O2 binding (increased affinity).
A shift to the right= decreased affinity (more likely to give up); hb is getting rid of O2
A shift to left is increased= increased affinity; hb is picking up O2
2,3 DPG (diphosphateglycerate) important in extended hypoxia.
Fetal hb tends to bind more O2 (not sensitive to 2,3 DPG)
Bohr effect
The affinity of hb’s binding to O2 is inversely related to acidity and the [CO2]–> more O2 is released in tissues with high CO2 and low pH
CO2 transport in blood
CO2 is ~20x more soluble in blood than O2, diffuses right in , and ~93% of it is converted to carbonic acid (due to carbonic anhydrase in RBC); ~ 5-7% is dissolved directly into blood (as CO2) - this proportion can bind to plasma proteins or enter RBCs and bind hb, forming carbaminohemoglobin. Each hb can bind 4 CO2. As RBCs pass through the O2 rich pulmonary circulation (higher concentration gradient of O2), CO2 can easily disassociate from hb, being replaced by O2
Carbon monoxide (CO) can bind like CO2 but has greater affinity than either CO2 or O2 so it’s retained by hb. Treatment=ventilation with O2 to force off CO
Hadalene effect
States that deoxygenated blood has an increased ability to carry CO2. Oxygenated blood carries less CO2. Similar to Bohr effect- has to do primarily with the oxygenation state of the blood and how this affects its capacity for CO2. The Bohr effect more relates to how pH and CO2 affect the blood capacity for carrying O2.
Enzymes Catalyze Reactions
They increase chemical reaction rate, reduce the free energy ( amount of energy needed to be put in a system for S–> P) needed to drive a chemical reaction, increase the probability of reaction occurrence
There are multiple reactions between ES and EP; reactions can be bidirectional or unidirectional; can have single or multiple S
Enzyme properties and Terminology
Globular proteins (have pockets or active sites that bind to S [aa residues]; exception= catalytic RNAs), Substrate selective (E has conformational change with S binds), have coenzymes with weak interactions/low energy requirement, have cofactors (inorganic ions ( Cu, Mg, Zn, Fe), holoenzyme (complete catalytically active enzyme with coenzymes and cofactors bound), classified by reaction type (Oxidoreductase, transferase, hydrolase, lyase, isomerase, ligase)
Enzymes enhance reaction rates by reducing activation energy
E lower energy threshold; coenzymes form and bind create weak interactions with S and E; reduce amount of energy that must be in system, free energy produced exceeds threshold (drives chemical reaction from S–> P)
Enzyme mechanism
Without E, high threshold of free energy to produce product;
E covalently change chemical structure of S; S complementation (lock and key model) would increase free energy demand; E (complementary to TS) shift S into the transition state (reduces amount of energy to go from TS –> P); weak binding is optimal in the transition state; weak bonding releases free energy (energy is exceeded which leads to production of P); weak binding drives enzyme catalysis (due to the release of energy, drives reaction from TS–> P)
Enzymes overcome Activation Barriers
Activation Barriers: 1. Entropy of molecules in solution (need S to bind pocket in E/be at right place at right time), 2. solvation shell (water) 3. substrate conformation (needs to change structure) 4. substrate orientation (specific)
Binding Energy: 1. Organize substrates, reduce entropy (creates free energy that drives reaction forward) 2. weak bonds desolvate substrates (water shell is peeled off, and S can be accessed) 3. weak bonds alter conformation (make it favorable to interact with dif. things) 4. E induced fit (room for S to bind)
G6P to F6P reaction
G6P–> binding to PHOSPHOHEXOSE ISOMERASE[changes structure of S] and opening of ring –> proton abstraction by active site (Glu is a base) leads to cis- enediol formation –> General acid catalysis by same Glu facilitates formation of F6P –> Dissociation (not as favorable to stay open) and closing of the ring
Reorganization of H and C bonds; all made possible by the active site (glutamate); ability of electrons to be moved in presence of H
Enzyme Kinetics regulate product formation
kinetics (rate at which E creates P)
Kinetic studies allow identification of mechanism, rate limiting steps of product formation , identification of inhibitors
E reduces free energy and speeds up reaction
Velocity
the primary measure of reaction rate; initial velocity is the velocity of onset when E meets S; max velocity is the max turnover rate that E can have based on [S] and [E] (The rate of reaction when the E is saturated with S is the maximum rate of reaction; how fast E can catalyze rxn)
V is affected by E, S, cofactors/coenzymes, E modifications, pH, temp
Michaelis Menten Kinetics
MM constant (km) is the [S] at which the initial reaction velocity (Vo) equals 1/2 the max reaction velocity (Vmax)
Km tells us how effective an E is at turning over P from a given [S] (binding affinity)
Vo= (Vmax [S]) /(Km + [S])
Assumptions: Single S- E rxn, free diffusion of S, [S] is below Vmax, constant conditions
Enzymes Catalyze Multiple Substrates along diverse Pathways
- Enzyme rxn involving a ternary (3 dif. molecules bound together ES1S2) complex (Random order or Ordered)
- Enzyme rxn in which no ternary complex is formed
ES1 –> EP1–> E’–> ES2
Irreversible Inhibition
Inhibitor covalently binds to E, preventing function and leading to degradation ex. Suicide (only way to produce function is to add more E)
Reversible Inhibition
Inhibitor binds the E or S to temporarily affect catalysis
ex. Competitive, Uncompetitive, Mixed, and Noncompetitive (rare; Vmax but not Km reduced)
Competitive Inhibition
I binds E at same binding pocket as S which prevents S from binding to E; Competing for the same site; move curve to right (INCREASES Km (less efficient), but does not affect Vmax- if you increase [S] can still get to Vmax)
Uncompetitive Inhibition
I binds to ES complex; binds to different site than S; reduces turnover rate or effectiveness of E from going to S–> P; Km is slightly changed (reduced), but reduction of Vmax (max amount of S that is converted to P is reduced)
Mixed Inhibition
Separate binding site from S; may bind S or E; Km shifted to right and Vmax reduced (changes likelihood of S binding E (Km) and also whether or not reaction occurs(Vmax); Inhibitor can compete and reduce number of E available
Allosteric Enzyme have flexible catalytic activity
E conformation is changed by effector binding; regulatory modifications alter catalytic function; increased or decreased activity, do not follow MM kinetics (changes catalytic function); complex protein structures; E with 2 dif. parts- modulator that binds dif part E that makes it more active; increases it’s affinity for S and therefore activity of E
Allosteric Enzymes are post translationally modified
Changing structure of E itself (covalently modified- target residues) leads to allosteric modulation ex. adding Pi, methyl group, etc.
Allosteric Enzymes do not follow MM Kinetics
Homotropic Regulation- S regulates E function
Heterotropic Regulation- Non- S molecules regulate E function
Regulation occurs at a separate site from S binding; change chemical structure of E itself instead of just binding
Enzyme drives metabolism and signal transduction
Changes in E rate and function are regulated; production of energy from citric acid cycle for example- all are E that are changed structure of one protein to next; changing its structure to become more active and changes structure of another protein; E functions in chains; allosteric; important for a biochemical pathway to go forward or be inhibited
The blood system
Important functions: Gas exchange (O2 from lungs to tissue), immunity, tissue repair and regeneration, tissue homeostasis
Diverse and disparate cell types
Discontinuous (not connected, spread throughout body) but targeted
Broad localization
Blood system components
Plasma (55%): Nutrients (water- 92%), waste, signaling
RBC (45%): 4-5 mil/µL, O2 transport, CO2 conversion
WBC: 3,500- 10,000/µL, immunity, clotting and repair, signaling
Platelets: 150,000- 450,000/µL, hemostasis (ensures viability of vasculature; maintenance and repair)
Hematopoesis creates blood cells
erythrocytes- RBC, leukocytes- WBC (lymphocytes, monocytes, granulocytes), platelets; bone marrow production and peripheral maturation
Blood cells are produced in the bone marrow
Stem cells, progenitor cells and blast cells; constant production, organized, most cells mature in the periphery, biopsy assesses blood system health (cluster of cell around dif. sinuses, how productive cells are), can be depleted (radiation, chemically, etc.) and replaced (bone marrow transplantation)
RBC transport O2
Packed with hemoglobin (hb) [move O2 to appropriate tissues]; carbonic anhydrase (CO2 exchange [CO2–> bicarbonate]); high surface area to volume ratio (small but concave disc shape), flexible (due to shape), roughly 7µm in size, no nucleus or organelles, hematocrit (erythrocyte blood count- between 40-50%); lifespan of roughly 120 days , with 1-2% replaced daily; Erythropoesis driven by the hormone erythropoietin (EPO); hypoxia increases lactic acid (glycolysis in anaerobic conditions) and EPO production to make more RBC; requires iron (for hb), folic acid (vit B9) and cobalamin (vit B12) [production and function of RBC requires these]
Neutrophils are immune system first responders
Primary inflammatory cell, stored in bone marrow until needed, granulocyte, multi- lobed nuclei, antimicrobial granules with growth factors, antimicrobial substances like proteins and lipids, several effector mechanisms (phagocytosis, degranulation (exocytosis), net formation (capture pathogens in tissue but more commonly in vasculature); restricted to the vasculature (can move into tissues to destroy pathogens), must be recruited to site of inflammation; built to die (effector mechanisms lead to cell death)
Granulocytes release antimicrobial peptides
Dense granules (antimicrobials, neurotransmitters [activate pain neurons], pro-inflammatory signals, growth factors); degranulation upon activation, predominantly reside in peripheral tissue, respond to parasites and worms
Granulocytes release antimicrobial peptides
Dense granules (antimicrobials, neurotransmitters [activate pain neurons], pro-inflammatory signals, growth factors); degranulation upon activation, predominantly reside in peripheral tissue, respond to parasites and worms ex. mast cells (packed with histamines), eosinophils, basophils
Monocytes activate the adaptive immune system
monocytes differentiate into macrophages (kill but do not die upon phagocytosis) or dendritic cells (DC); kill pathogens, clear debris, phagocytose antigens (immune system gets targeted against; ca be peptide, lipid, etc.) within periphery [ then move to lymph nodes] ; activate adaptive immune system (lymphocytes)
Lymphocytes are targeted, adaptive killers
T cells, B cells, and NK cells; adaptive immune system; cellular ( T and NK) while humoral (B- produce antibodies that bind to pathogens and signal others to be active); pathogens and diseased self tissue ; immune memory (basis for immunization), often require monocyte (DC or macrophage) activation
Megakaryocytes produce platelets
reside in bone marrow; secrete platelets ( small, cell fragments; organelles but no nucleus; involved in hemostasis (maintain integrity of vasculature), needed for clot formation/ removal; forms plugs, contain protein rich granule (with growth factors, pro inflammatory factors for repair of tissue); involved in the inflammatory response (form and breakdown clots), structural- protein dense
Hemostasis- Preventing blood loss
Mechanisms
- Vascular constriction (smooth muscles contract, prevent blood flow, [opposite of inflammatory response])
- platelet plug (platelets agglutinate, closes small ruptures)
- Coagulation (Fibrin matrix formation, fibroblast recruitment, wound healing and clot removal)
Severed vessel–> platelet agglutination–> fibrin appears –> Fibrin clot forms –> Clot retraction occurs
The coagulation pathway
Seals large vessel ruptures, occurs at the blood tissue interface, components produced in the liver and circulate in the blood, coagulation is initiated by the production of thrombin (weak protease), weak but dense fibrin fiber mesh is formed (stabilized by activated fibrin- stabilizing factor), clot collects platelets, erythrocytes, leukocytes; occurs within seconds to minutes (stabilized fibers formed); serum is plasma with clotting factors removed; prothrombin activator is the rate limiting step (activated by intrinsic or extrinsic pathways)
2 Pathways produce Prothrombin Activator
Intrinsic pathway- begins in the blood
Extrinsic pathway- begins at the site of tissue trauma
Most factors are proteases (cleave structure of second structure, protein that cleaves another protein), vitamin K is absolutely essential (cofactor- affects enzymatic activity), fibrolysis degrades the fibrin meshwork, both pathways function simultaneously
