Файл: Kaplan USMLE-1 (2013) - Anatomy.pdf

Clinical Correlate

The parotid gland is the major site of the mumps and rabies viruses that are transmitted in saliva.

Benign tumors most frequently appear at the parotid gland; their removal

is complicated by the facial nerve traversing the gland.

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Figure 1-8-10. Submandibular with a mix of light-staining mucus acini (arrow) adjacent to dark-staining serous acini

Small vessels (arrowheads)

•The parotid glands lie on the surface ofthe masseter muscles in the lateral face, in front of each external auditory meatus. The parotids are entirely serous salivary glands that drain inside each cheek through Stensen's ducts which open above the second upper molar tooth. The parotid glands contribute 25% of the volume of saliva.

•The submandibular glands lie inside the lower edge of the mandible, and are mixed serous/mucous glands with a predominance ofserous cells. They drain in the floor of the mouth near the base of the tongue through Wharton's ducts. The submandibular glands contribute 70% of the volume of saliva.

•The sublingual glands lie at the base of the tongue, and are also mixed serous/mucous glands with a predominance ofmucous cells. They drain into the mouth through multiple small ducts, The sublingual glands contribute 5% of the volume of saliva.

Exocrine Pancreas

The pancreas is a branched tubuloacinar exocrine gland with acini. The acini are composed ofsecretory cells that produce multiple digestive enzymes includ­ ing proteases, lipases, and amylases. Acinar cells are functionally polarized, with basophilic RER at their basal ends below the nucleus, and membrane-bound, enzyme-containing eosinophilic zymogen granules toward their apex.

explain the differential effect on hepatocytes of changes in blood flow, oxy­ genation, etc. Zone 3 is most susceptible to injury by decreased oxygenation of blood or decreased blood flow into the liver (as well as stagnation of blood drainage out ofthe liver due to congestive heart failure).

The metabolic activity of hepatocytes varies within the zones of the acinus. Zone 1 hepatocytes are most involved in glycogen synthesis and plasma pro­ tein synthesis (albumin, coagulation factors and complement components). Zone 3 cells are most concerned with lipid, drug, and alcohol metabolism and detoxification.

Different functions of the hepatocyte are concentrated in different organelles.

•Rough endoplasmic reticulum (RER) is responsible for protein synthesis

(e.g., albumin, coagulation. factors, complement components, and lipo­ proteins).

•Smooth endoplasmic reticulum (SER) has many enzymes associated with its membranes and is responsible for synthesis of cholesterol and bile acids, conjugation (solubilization) of bilirubin and lipid soluble drugs, formation of glycogen under control of insulin (glycogen rosettes are often associated with SER) and breakdown of glycogen to glucose (glycogenolysis) under the control of glucagon and epinephrine, and detoxification of lipid soluble drugs (e.g., phenobarbital), including via the microsomal enzyme oxidizing system (MEOS).

•The Golgi apparatus is responsible for glycosylation of proteins and packaging some proteins for secretion.

•Lysosomes are responsible for degradation of aged plasma glycoproteins taken up from the blood.

•Peroxisomes are responsible for breakdown of hydrogen peroxide.

Ito cells (stellate cells) are mesenchymal cells that live in the space of Disse. They contain fat and are involved in storage of fat-soluble vitamins, mainly vitamin A.

Bile formation by hepatocytes serves both an exocrine and excretory function. Bile salts secreted into the duodenum aid in fat emulsification and absorption, as well as excretion of endogenous metabolites (bilirubin) and drug metabolites that cannot be excreted by the kidney. Bile consists ofa mixture ofbilesalts (con­ jugated bile acids), conjugated bilirubin (and other conjugated endogenous or drug metabolites), cholesterol, phospholipids, electrolytes, and water.

Bile acids are synthesized from cholesterol by hepatocytes, and subsequently conjugated in SER to produce bile salts. Specific transporters at the bile cana­ liculus secrete bile salts into bile Within the gut lumen some bile salts are par­ tially metabolized by gut bacteria to produce other bile salts (deoxycholic and lithocholic acid). All ofthese bile salts can be reabsorbed, principally in the small intestine, and recycled in bile (the enterohepatic circulation ofbile).

The liver excretes bilirubin, a metabolic breakdown product of hemoglobin from old red blood cells. Bilirubin is not very water-soluble, and is transported in plasma bound to protein, chiefly albumin. Hepatocytes have specific transport proteins that import bilirubin into their cytoplasm, where the hepatocytes then "solubilize" the bilirubin by conjugating it, chiefly to glucuronic acid. This solu­ bilized form ofbilirubin is then secreted into bile by a specific transport system at the canaliculus.

Clinical Correlate

When stimulated during liver injury, Ito cells may release type I collagen and other matrix components into the

space of Disse, contributing to scarring ofthe liver in some diseases (cirrhosis due to ethanol). This may lead to the development of portal hypertension, portacaval anastomoses, and esophageal or rectal bleeding.

Clinical Correlate

Disturbance of the balance in the components of bile can lead to precipitation of one or more ofthe bile components, resulting in stone (or calculus) formation or lithiasis in the gallbladder and/or bile ducts.

Clinical Correlate

The absence of nephrin protein renders podocytes incapable of forming foot processes and slit diaphragms, and results in a congenital nephrotic syndrome, NPHSl.

Figure 1-9-6 Transmission electron micrograph demonstrating podocytes

Blood plasma is filtered from the lumen of the capillary to the urinary space across the combined capillary endothelium-podocyte complex. Fenestrations in the endothelium are large (50-100 nm) and occupy 20% of the capillary surface. Fenestrations block the exit of cells, but allow free flow of plasma. The shared basal lamina ofpodocytes and endothelium constitutes the first, coarser filtration barrier; it blocks the passage of molecules larger than 70 kD.

The thin diaphragms covering the slit openings between the podocyte foot pro­ cesses constitutes a more selective filter. The slits are composed ofelongated pro­ teins which arise from the surface of the adjacent foot process cell membranes and join in the center of the slit, in a zipper-like configuration. The width of the junction between 2 adjacent podocytes varies between 20 and 50 nm, possibly as a function ofperfusion pressures ofthe glomerulus.

The major protein components of the slit diaphragm are specific (nephrin, podocyn) and generic components of other cell junctions (cadherins).

Podocyte foot processes are motile (they contain actin and myosin). They are connected to each other by the slit diaphragm and to the basal lamina. The slit diaphragm molecular complex is associated with the actin cytoskeleton. Altera­ tions in composition and/or arrangement of these complexes are found in many forms ofhuman and experimental diseases.

Large, negatively charged complexes in the basal lamina and the lateral surfaces ofthe podocyte feet help to slow diffusion ofnegatively charged molecules (such as albumin) across the lamina, and may help the uptake of positively charged

Proximal Convoluted Tubule

The proximal convoluted tubule (PCT) opens at the urinary pole of Bowman's capsule. The PCT follows a circuitous path and ends with a straight segment that connects to the loop of Henle. PCT cells are tall, and they have a pink cytoplasm, long apical microvilli, and extensive basal invaginations. Numerous large mi­ tochondria are located between the basal invaginations. The lateral borders of adjacent cells are extensively interdigitated. These characteristics are typical of cells involved in active transport. The lumen ofthe PCT is frequently clouded by microvilli which do not preserve well during the histologic preparation process.

Loop of Henle

The loop of Henle has a smaller diameter than the PCT and has descending and ascending limbs which go in opposite directions. Some loops of Henle have a wider segment before the distal tubule. The straight and convoluted segments of the distal convoluted tubule (DCT) follow. The straight portions of the PCT and DCT have traditionally been assigned to the loop ofHenle (constituting the thick ascending and descending limbs) but they are now thought to be part ofthe PCT and DCT to which they are more similar. The special disposition of the loops of Henle descending and ascending branches, coupled with their specific transport and permeability properties, allow them to operate as "countercurrent multipli­ ers;' creating a gradient ofextracellular fluid tonicity in the medulla. This is used to modulate urine tonicity and finalvolume.

Distal Convoluted Tubule

The DCT comes back to make contact with its own glomerulus, and then con­ nects to the collecting tubule, which receives urine from several nephrons and is open at its far end. The epithelium of DCT, loops of Henle, and collecting ducts have variable thicknesses and more or less well-defined cell borders. Some have limited surface microvilli. In general, these tubes either do much less active trans­ port than the PCT or are involved only in passive water movements.

Collecting Ducts

Collecting ducts are linedbyprincipal cells and intercalated cells. The cell outline of these cells is more distinct than that of the PCT or the DCT. Principal cells respond to aldosterone.

Mesangial Cells

Mesangial cells (also known as Polkissen or Lacis cells) are located between capil­ laries, under the basal lamina but outside the capillary lumen. There is no basal lamina between mesangial and endothelial cells. Mesangial cells are phagocytic and may be involved in the maintenance of the basal lamina. Abnormalities of mesangial cells are detected in several diseases resulting in clogged and/or dis­ torted glomeruli.

Note

Renal cortex and medullary fibroblasts (interstitial cells) produce erythropoetin.

Note

Diuretics act by inhibiting Na+ resorption, leading to an increase in Na+ and water excretion.