The pancreas

The pancreas consists of clusters if endocrine cells (the islets of Langerhans) and exocrine cells whose secretions drain into the duodenum.

Pancreatic fluid contains:

• sodium bicarbonate (NaHCO₃). This neutralizes the acidity of the fluid arriving from the stomach raising its pH to about 8.
• pancreatic amylase. This enzyme hydrolyzes starch into a mixture of maltose and glucose.
• pancreatic lipase. The enzyme hydrolyzes ingested fats into a mixture of fatty acids and monoglycerides. Its action is enhanced by the detergent effect of bile.
• 4 zymogens— proteins that are precursors to active proteases. These are immediately converted into the active proteolytic enzymes:
  • trypsin. Trypsin cleaves peptide bonds on the C-terminal side of arginines and lysines.
  • chymotrypsin. Chymotrypsin cuts on the C-terminal side of tyrosine, phenylalanine, and tryptophan residues (the same bonds as pepsin, whose action ceases when the NaHCO₃ raises the pH of the intestinal contents).
  • elastase. Elastase cuts peptide bonds next to small, uncharged side chains such as those of alanine and serine.
  • carboxypeptidase. This enzyme removes, one by one, the amino acids at the C-terminal of peptides.
• nucleases. These hydrolyze ingested nucleic acids (RNA and DNA) into their component nucleotides.

The secretion of pancreatic fluid is controlled by two hormones:

• secretin, which mainly affects the release of sodium bicarbonate, and
• cholecystokinin (CCK), which stimulates the release of the digestive enzymes.

Principal heart sounds

1. S1: closure of AV valves;typically auscultated as a single sound 

Clinical note: In certain circumstances, S1 may be accentuated. This occurs when the valve leaflets are “slammed” shut in early systole from a greater than normal distance because they have not had time to drift closer together. Three conditions that can result in an accentuated S1 are a shortened PR interval, mild mitral stenosis, and high cardiac-output states or tachycardia.

2. S2: closure of semilunar valves in early diastole , normally “split” during inspiration . S2: best appreciated in the 2nd or 3rd left intercostal space

Clinical note: Paradoxical or “reversed” splitting occurs when S2 splitting occurs with expiration and disappears on inspiration. Moreover, in paradoxical splitting, the pulmonic valve closes before the aortic valve, such that P2 precedes A2. The most common cause is left bundle branch block (LBBB). In LBBB, depolarization of the left ventricle is impaired, resulting in delayed left ventricular contraction and aortic valve closure.

3. S3: ventricular gallop, presence reflects volume-overloaded state 
 
 Clinical note: An S3 is usually caused by volume overload in congestive heart failure. It can also be associated with valvular disease, such as advanced mitral regurgitation, in which the “regurgitated” blood increases the rate of ventricular filling during early diastole.
 
4. S4: atrial gallop, S4: atrial contraction against a stiff ventricle, often heard after an acute myocardial infarction.

Clinical note: An S4 usually indicates decreased ventricular compliance (i.e., the ventricle does not relax as easily), which is commonly associated with ventricular hypertrophy or myocardial ischemia. An S4 is almost always present after an acute myocardial infarction. It is loudest at the apex with the patient in the left lateral decubitus position (lying on their left side).

The nephron of the kidney is involved in the regulation of water and soluble substances in blood.

A Nephron

A nephron is the basic structural and functional unit of the kidneys that regulates water and soluble substances in the blood by filtering the blood, reabsorbing what is needed, and excreting the rest as urine.

 Its function is vital for homeostasis of blood volume, blood pressure, and plasma osmolarity.

It is regulated by the neuroendocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

The Glomerulus

The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation. Here, fluid and solutes are filtered out of the blood and into the space made by Bowman's capsule.

A group of specialized cells known as juxtaglomerular apparatus (JGA) are located around the afferent arteriole where it enters the renal corpuscle. The JGA secretes an enzyme called renin, due to a variety of stimuli, and it is involved in the process of blood volume homeostasis.

The Bowman's capsule surrounds the glomerulus. It is composed of visceral (simple squamous epithelial cells; inner) and parietal (simple squamous epithelial cells; outer) layers.

Red blood cells and large proteins, such as serum albumins, cannot pass through the glomerulus under normal circumstances. However, in some injuries they may be able to pass through and can cause blood and protein content to enter the urine, which is a sign of problems in the kidney.

Proximal Convoluted Tubule

The proximal tubule is the first site of water reabsorption into the bloodstream, and the site where the majority of water and salt reabsorption takes place. Water reabsorption in the proximal convoluted tubule occurs due to both passive diffusion across the basolateral membrane, and active transport from Na+/K+/ATPase pumps that actively transports sodium across the basolateral membrane.

Water and glucose follow sodium through the basolateral membrane via an osmotic gradient, in a process called co-transport. Approximately 2/3rds of water in the nephron and 100% of the glucose in the nephron are reabsorbed by cotransport in the proximal convoluted tubule.

Fluid leaving this tubule generally is unchanged due to the equivalent water and ion reabsorption, with an osmolarity (ion concentration) of 300 mOSm/L, which is the same osmolarity as normal plasma.

The Loop of Henle

The loop of Henle is a U-shaped tube that consists of a descending limb and ascending limb. It transfers fluid from the proximal to the distal tubule. The descending limb is highly permeable to water but completely impermeable to ions, causing a large amount of water to be reabsorbed, which increases fluid osmolarity to about 1200 mOSm/L. In contrast, the ascending limb of Henle's loop is impermeable to water but highly permeable to ions, which causes a large drop in the osmolarity of fluid passing through the loop, from 1200 mOSM/L to 100 mOSm/L.

Distal Convoluted Tubule and Collecting Duct

The distal convoluted tubule and collecting duct is the final site of reabsorption in the nephron. Unlike the other components of the nephron, its permeability to water is variable depending on a hormone stimulus to enable the complex regulation of blood osmolarity, volume, pressure, and pH.

Normally, it is impermeable to water and permeable to ions, driving the osmolarity of fluid even lower. However, anti-diuretic hormone (secreted from the pituitary gland as a part of homeostasis) will act on the distal convoluted tubule to increase the permeability of the tubule to water to increase water reabsorption. This example results in increased blood volume and increased blood pressure. Many other hormones will induce other important changes in the distal convoluted tubule that fulfill the other homeostatic functions of the kidney.

The collecting duct is similar in function to the distal convoluted tubule and generally responds the same way to the same hormone stimuli. It is, however, different in terms of histology. The osmolarity of fluid through the distal tubule and collecting duct is highly variable depending on hormone stimulus. After passage through the collecting duct, the fluid is brought into the ureter, where it leaves the kidney as urine.

• Sensory:
  • Somatic (skin & muscle) Senses:
    Postcentral gyrus (parietal lobe). This area senses touch, pressure, pain, hot, cold, & muscle position. The arrangement is upside-down (head below, feet above) and is switched from left to right (sensations from the right side of the body are received on the left side of the cortex). Some areas (face, hands) have many more sensory and motor nerves than others. A drawing of the body parts represented in the postcentral gyrus, scaled to show area, is called a homunculus .
  • Vision:
    Occipital lobe, mostly medial, in calcarine sulcus. Sensations from the left visual field go to the right cortex and vice versa. Like other sensations they are upside down. The visual cortex is very complicated because the eye must take into account shape, color and intensity.
  • Taste:
    Postcentral gyrus, close to lateral sulcus. The taste area is near the area for tongue somatic senses.
  • Smell:
     The olfactory cortex is not as well known as some of the other areas. Nerves for smell go to the olfactory bulb of the frontal cortex, then to other frontal cortex centers- some nerve fibers go directly to these centers, but others come from the thalamus like most other sensory nerves
  • Hearing:
    Temporal lobe, near junction of the central and lateral sulci. Mostly within the lateral sulcus. There is the usual crossover and different tones go to different parts of the cortex. For complex patterns of sounds like speech and music other areas of the cortex become involved.
• Motor:
  • Primary Motor ( Muscle Control):
    Precentral gyrus (frontal lobe). Arranged like a piano keyboard: stimulation in this area will cause individual muscles to contract. Like the sensory cortex, the arrangement is in the form of an upside-down homunculus. The fibers are crossed- stimulation of the right cortex will cause contraction of a muscle on the left side of the body.
  • Premotor (Patterns of Muscle Contraction):
    Frontal lobe in front of precentral gyrus. This area helps set up learned patterns of muscle contraction (think of walking or running which involve many muscles contracting in just the right order).
  • Speech-Muscle Control:
    Broca's area, frontal lobe, usually in left hemisphere only. This area helps control the patterns of muscle contraction necessary for speech. Disorders in speaking are called aphasias.
• Perception:
  • Speech- Comprehension:
    Wernicke's area, posterior end of temporal lobe, usually left hemisphere only. Thinking about words also involves areas in the frontal lobe.
  • Speech- Sound/Vision Association:
    Angular gyrus, , makes connections between sounds and shapes of words

Serum Lipids

• Total cholesterol is the sum of
  • HDL cholesterol
  • LDL cholesterol and
  • 20% of the triglyceride value
• Note that
  • high LDL values are bad, but
  • high HDL values are good.
• Using the various values, one can calculate a
  cardiac risk ratio = total cholesterol divided by HDL cholesterol
• A cardiac risk ratio greater than 7 is considered a warning.

The pituitary gland is pea-sized structure located at the base of the brain. In humans, it consists of two lobes:

• the Anterior Lobe and
• the Posterior Lobe

The Anterior Lobe

The anterior lobe contains six types of secretory cells All of them secrete their hormone in response to hormones reaching them from the hypothalamus of the brain.

Thyroid Stimulating Hormone (TSH)

TSH (also known as thyrotropin) is a glycoprotein The secretion of TSH is

• stimulated by the arrival of thyrotropin releasing hormone (TRH) from the hypothalamus.
• inhibited by the arrival of somatostatin from the hypothalamus.

 TSH stimulates the thyroid gland to secrete its hormone thyroxine (T₄).

Some develop antibodies against their own TSH receptors making more T₄ causing hyperthyroidism. The condition is called thyrotoxicosis or Graves' disease.

Hormone deficiencies

A deficiency of TSH causes hypothyroidism: inadequate levels of T₄ (and thus of T₃ )..

Follicle-Stimulating Hormone (FSH)

FSH is a heterodimeric glycoprotein Synthesis and release of FSH is triggered by the arrival from the hypothalamus of gonadotropin-releasing hormone (GnRH).

FSH in females :In sexually-mature females, FSH (assisted by LH) acts on the follicle to stimulate it to release estrogens.

FSH in males :In mature males, FSH acts on spermatogonia stimulating (with the aid of testosterone) the production of sperm.

Luteinizing Hormone (LH)

LH is synthesized within the same pituitary cells as FSH and under the same stimulus (GnRH). It is also a heterodimeric glycoprotein

LH in females

In sexually-mature females, LH

• stimulates the follicle to secrete estrogen in the first half of the menstrual cycle
• a surge of LH triggers the completion of meiosis I of the egg and its release (ovulation) in the middle of the cycle
• stimulates the now-empty follicle to develop into the corpus luteum, which secretes progesterone during the latter half of the menstrual cycle.

LH in males

LH acts on the interstitial cells (also known as Leydig cells) of the testes stimulating them to synthesize and secrete the male sex hormone, testosterone.

LH in males is also known as interstitial cell stimulating hormone (ICSH).

Prolactin (PRL)

Prolactin is a protein of 198 amino acids. During pregnancy it helps in the preparation of the breasts for future milk production. After birth, prolactin promotes the synthesis of milk.

Prolactin secretion is

• stimulated by TRH
• repressed by estrogens and dopamine.

Growth Hormone (GH)

• Human growth hormone (also called somatotropin) is a protein
• The GH-secreting cells are stimulated to synthesize and release GH by the intermittent arrival of growth hormone releasing hormone (GHRH) from the hypothalamus. GH promotes body growth

In Child

• hyposecretion of GH produces dwarfism
• hypersecretion leads to gigantism

In adults, a hypersecretion of GH leads to acromegaly.

ACTH — the adrenocorticotropic hormone

ACTH acts on the cells of the adrenal cortex, stimulating them to produce

• glucocorticoids, like cortisol
• mineralocorticoids, like aldosterone
• androgens (male sex hormones, like testosterone

Hypersecretion of ACTH cause of Cushing's disease.