(a) Explain the basic stimuli causing pancreatic secretion. Discuss the role of pancreas in major food digestion. 20 (b) Explain…

(a) Stimuli of pancreatic secretion and role of the pancreas in digestion

Stimuli (three overlapping phases)

• Cephalic phase: sight, smell, taste and chewing act through the vagus and cause a small, enzyme-rich secretion from acinar cells.
• Gastric phase: gastric distension acts through vagovagal reflexes and adds a modest enzyme-rich secretion.
• Intestinal phase (the major one, about 70–80%): acid chyme in the duodenum (pH below about 4.5) stimulates S cells to release secretin, which acts on duct cells to give a large volume of watery, bicarbonate-rich juice that neutralises acid and gives the enzymes an alkaline pH (about 7–8). Fatty acids, monoglycerides, peptides and amino acids stimulate I cells to release cholecystokinin (CCK), which acts on acinar cells, partly through vagal afferents, to give enzyme-rich secretion and also contracts the gallbladder. Secretin and CCK potentiate each other.

Role in digestion

• Carbohydrate: pancreatic α-amylase cleaves internal α-1,4 bonds of starch and glycogen to maltose, maltotriose and α-limit dextrins; the brush-border enzymes finish the job.
• Protein: trypsinogen is activated to trypsin by enteropeptidase (enterokinase) of the duodenal brush border; trypsin then activates chymotrypsinogen, proelastase and procarboxypeptidases (and more trypsinogen). Trypsin, chymotrypsin and elastase are endopeptidases, and carboxypeptidases are exopeptidases; the products are oligopeptides and amino acids. Pancreatic trypsin inhibitor in the juice guards against premature activation inside the gland.
• Fat: pancreatic lipase, with colipase and bile salts, hydrolyses triglycerides to free fatty acids and 2-monoglycerides, which form micelles and are absorbed. The juice also contains phospholipase A2, cholesterol esterase and nucleases (ribonuclease, deoxyribonuclease).
• The pancreas is thus the main source of digestive enzymes for all three food groups, and its bicarbonate makes the duodenal medium suitable for them.

(b) Oxygen transport and shifts of the dissociation curve

Transport

• About 98.5% of O2 is carried as oxyhaemoglobin and about 1.5% (roughly 0.3 mL per 100 mL blood) as dissolved O2, which sets the pO2 that drives loading.
• Haemoglobin is a tetramer (two α and two β chains), each with a haem iron that binds one O2; fully saturated, 1 g binds about 1.34 mL O2.
• Binding is cooperative: oxygenation of one subunit shifts the tetramer from the tense (T, low-affinity) to the relaxed (R, high-affinity) state, so the curve is sigmoid. Loading at the lungs (pO2 about 100 mmHg, saturation about 97–98%) and unloading in tissues (pO2 about 40 mmHg, saturation about 75%) both occur on the steep part. P50 is about 26–27 mmHg.

Shifts of the curve

• Right shift (lower affinity, easier unloading): raised pCO2, fall in pH (Bohr effect), raised temperature and raised 2,3-bisphosphoglycerate (2,3-BPG). These occur in active muscle; 2,3-BPG also rises at altitude and in chronic hypoxia.
• Left shift (higher affinity, harder unloading): fall in pCO2, rise in pH, lower temperature and lower 2,3-BPG, as in lungs. Fetal haemoglobin (α2γ2) binds 2,3-BPG poorly and so has a left-shifted curve, favouring transfer from mother to fetus. Carbon monoxide shifts the curve left and also lowers carrying capacity. Stored blood low in 2,3-BPG shows left shift.
• Effect of CO2 and H+ on binding is the Bohr effect; the converse effect of O2 on CO2 carriage is the Haldane effect.

(c) Functional anatomy of the cochlea and functions of the organ of Corti

Anatomy (see the labelled cross-section below)

• The cochlea is a bony spiral of about 2.5–2.75 turns around the modiolus, divided into three scalae. Scala vestibuli (from the oval window) and scala tympani (ending at the round window) hold perilymph and meet at the helicotrema at the apex. Scala media (cochlear duct) holds endolymph, which is rich in K+ and has a positive potential of about +80 mV; it is separated from scala vestibuli by Reissner's (vestibular) membrane and from scala tympani by the basilar membrane. The stria vascularis secretes endolymph.
• Function: the stapes at the oval window sets up pressure waves in perilymph, and the round window bulges out to release the pressure. The basilar membrane is narrow and stiff at the base and wide and flexible at the apex, so a travelling wave peaks near the base for high frequencies and near the apex for low ones (place coding).

Organ of Corti (on the basilar membrane)

• It has one row of inner hair cells (about 3,500) and three rows of outer hair cells (about 12,000), with pillar cells, Deiters' and other supporting cells, and the overlying tectorial membrane.
• Stereocilia of hair cells are deflected by shearing against the tectorial membrane; K+ enters through mechanically gated channels and depolarises the cell. Ca2+ entry releases glutamate onto spiral ganglion fibres of the cochlear nerve.
• Inner hair cells are the true sensory receptors, with about 90–95% of afferent fibres. Outer hair cells, through the motor protein prestin, change length and amplify and sharpen the basilar-membrane response; they also receive efferent fibres.
• The organ of Corti thus transduces mechanical vibration into neural signals and encodes pitch (place) and loudness.