E STUDY 5-1 UNDER THE MICROSCOPE FOCUSING IN Members of the clinically significant group of parasites located in blood and tissue that move by means of flagella, known as the hemoflagel lates, belong to the genera Leishmania and Try panosoma. There are four morphologic forms of clinical significance associated with these hemo flagellates: amastigote, promastigote, epimasti gote, and trypomastigote, all of which are defined and described in detail in this chapter. Although the specific life cycle may vary, all the organisms in these two genera involve some combination of the four morphologic forms. The transmission of all hemoflagellates is via the bite of an arthropod vector. The major difference between the two genera is the primary diagnostic form found in each; for Leishmania it is the amastigote and for Trypanosoma it is the trypomastigote, with the exception of Trypanosoma cruzi, in which amas tigotes may also be found. Speciation within the genera usually depends heavily on the patient importance of this information, this text pro vides a discussion of the geographic distribution and symptomatology of each hemoflagellate. Suspicions of hemoflagellate disease processes are typically confirmed by more advanced diag nostic techniques, such as serologic tests. Because the initial diagnosis of hemoflagellate infections relies primarily on the detection of the morpho logic forms, this text will begin with a detailed discussion of the morphologic forms. MORPHOLOGY AND LIFE CYCLE NOTES Morphology Amastigotes. The average roundish to oval amastigote measures 5 by 3 μm in size (Figs. 51 and 5-2; Table 5-1). The amastigote contains a nucleus, a basal body structure (called a blepha roplast), and a small parabasal body. The large single nucleus is typically located offcenter, sometimes present more toward the edge of the Nineyearold Chares, an African boy, recenty emigrated to the United States from Kenya with his family. He began complaining of chills and diarrhea 2 weeks prior to the office vsit. After taking his temperature, whch revealed a fever, hs mother took him into his pediatrician’s office. During the examination, the doctor found a skn leson on hs right arm and marked hepatosplenomegaly. A compete bood count (CBC) was ordered, which revealed that Charles was anemic. The doctor, afraid that the chid was experiencing dum dum fever (kalaazar), ordered a biopsy of the infected skin lesion and blood for parasite study. When the specimens were received in the laboratory, the laboratory technician on duty made slides of the skn lesion material and blood, stained them with Giemsa stan, and carefully examined the slides. No parastes were found in the bood slide The biopsy slide revealed an oval organ ism (see diagram); it contained one nuceus, a parabasal body, and an axonemelike structure. Questions for Consideration 1. What parasite do you suspect? (Objective 5-10B) 2. Which morphologic form of the parasit

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 SMALL INTESTINE AND LARGE INTESTINE-
DIGESTION AND ABSORPTION

2. SMALL INTESTINE
SECRETION
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 Mucus by Brunner’s glands in duodenum
 Stimuli: tactile, irritating, vagal, GI hormones
 Alkaline mucus: protection from gastric acid
 Inhibited by sympathetic stimulation…?duodenal
ulcers
 Intestinal digestive juices by Crypts of
Lieberkuhn:
 Goblet cells (mucus) & enterocytes (water &
electrolytes)
 1800mls/d; pH 7.5-8.0; creates watery vehicle
for absorption

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 Digestive
enzymes:
 Peptidases
 Dissacharidases
 Intestinal lipase
 Local regulation
 Intestinal
epithelium has a
life cycle of 5 days

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5. FUNCTION OF SMALL
INTESTINE
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 Secretion-
digestion,protection,activation,haemopeisis
 Hormonal
 Mechanical
 Absorption

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7. LARGE INTESTINE
SECRETION
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 Have crypts of Lieberkuhn that secrete only mucus and
a little HCO3
-
 Protects mucosa from: acids from bacterial activity and
physical excoriation.
 Mucus adheres feces together.
 Stimuli:
 Tactile by local reflexes
 Parasympathetic nervous system

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9. DIGESTION & ABSORPTION
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10. DIGESTION AND
ABSORPTION
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OBJECTIVES:
 To describe the site, digestive enzymes and
secretions involved in the digestion of:
 CHO’s, Proteins, Lipids
 To describe the absorbable units, transporters
involved and disorders in absorption of:
 CHO’s, Proteins, Lipids, Fluid & Electrolytes.

11. Introduction
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 Digestion and absorption is the ultimate
function of GIT.
 Digestion is the breakdown of ingested food
into absorbable particles.
 Absorption is movement of nutrients, water &
electrolytes from intestinal lumen into the
blood.
 Occurs through cellular or paracellular paths

12. The small intestine
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 Most of the absorption occurs here.
 The intestinal mucosa has longitudinal folds of
Kerckring, villi & microvilli.
 These increase absorptive surface area 600-1000
times.
 They contain epithelial cells interspersed with
goblet cells.
 Epithelial cells are shed every 3-6 days making
them vulnerable to irradiation and chemotherapy.

13. 1. CARBOHYDRATES
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 Almost all ingested foods have >50% CHO’s
 Contains polysaccharides (starch),
disaccharides (trehalase, maltose, sucrose &
lactose) and monosaccharide (glucose &
fructose).
 Absorbed only as monosaccharide.
 Digestion begins in the mouth and is as
follows:

14. For starch
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15. The disaccharides
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16. Cho’s absorption
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 Absorbed as monosaccharides.
 Glucose and galactose: through Na-dependent 20 active
transport against the gradient on the apical membrane.
 Fructose: by GLUT 5(fructose specific transporter) by
facilitated diffusion hence none against gradient.
 Once in the cell all are absorbed across basolateral
membrane via GLUT 2 by facilitated diffusion.

17. Lumen blood
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18. Lactose intolerance
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 A condition where there is absence of lactase and
one fails to breakdown lactose into glucose and
galactose.
 As such lactose is not absorbed and remains in
the lumen
 Being osmotic it retains water in the lumen and
leads to Diarrhea.
 Treatment: avoid milk products or lactase
supplementation.

19. 2. PROTEINS
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 Absorbable forms are amino acids, dipeptides and
tripeptides.
 This is facilitated by the proteases in stomach and
small intestine.
 In the stomach(pepsin), small intestines
(endopeptidases- trypsin, chymotrypsin, elastase
& exopeptidases- carboxypeptidase A&B)
 Pancreatic secretions which are mostly proteins
are also absorbed in the same manner.

20. Digestion
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 The pancreatic peptides are released in inactive
form.
 Trypsinogen is activated by enterokinase and the
resulting trypsin catalyzes the activation of the
other proteases including trypsinogen.
 Breakdown proteins to amino acids, dipeptides
and tripeptides.
 Finally the proteases digest themselves.

21. Activation of proteases
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23. Absorption
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 Absorbable in larger molecules than CHO’s
 Amino acids by the Na-aa co transporter each for
acidic, basic, neutral and imino amino acids.
 Most proteins are absorbed as di/tri peptides
through the H+ dependent transporter
 In the cells they are hydrolyzed by cytosolic
proteases to amino acids.
 On the basolateral membrane, there is facilitated
diffusion of aa’s and remaining di/tri peptides.

24. Figure 8-30
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25. Disorders of protein digestion &
absorption
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 Chronic pancreatitis
 Cystic fibrosis of the pancreas
 The two lead to failure in production of pancreatic
proteases and failed protein digestion.
 Cystinuria: involves absence of Na-aa co
transporter of basic aa’s in the kidney and GIT
 Leads to loss in urine and feces of cysteine,
lysine, arginine and ornithine.

26. 3. LIPIDS
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In the stomach:
 Lingual and gastric lipases
 Mixing and churning breakdown lipids further
 Dietary proteins emulsify lipids for lipases to
act
 Accounts for about 10% of all lipids.
 Delayed gastric emptying by CCK allows time
for duodenal digestion.

27. Small intestine
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 Bile salts: emulsify fats and help in micelles
formation
 Pancreatic lipase and colipase: breakdown
triglycerides
 Cholesterol ester hydroxylase: cholesterol esters
and triglycerides (glycerol)
 Phospholipase A2 : breaks phospholipids into
lysolecithin and fatty acids.
 Procollipase and prophospholipase A2 are
activated by trypsin.

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29. Disorders
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1) Pancreatic insufficiency (pancreatitis, fibrosis)
2) Duodenal acidity e.g. in ZE syndrome
3) Bile salts deficiency: resection of ileum
4) Bacterial overgrowth
5) Decreased intestinal cells e.g. tropical sprue
6) abetalipoproteinemia

30. 4.VITAMINS
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 Required in small quantities as cofactors or
coenzymes in metabolism.
 Not synthesized in the body hence gotten from
GIT
 Fat soluble vitamins:
 ADEK
 Absorbed as lipids.
 Incorporated into micelles….taken to
chylomicrons…to lymphatics…general
circulation

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 Water soluble vitamins:
 Vitamins C and B complex
 Absorbed through Na-dependent co transport
except vitamin B12.
 Vitamin B12 is absorbed in the terminal ileum with
the help of intrinsic factor and transcobalamine
transporters.
 Lack of intrinsic factor leads to????????
 Pernicious anemia.

32. 5.CALCIUM
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 1,25 dihydroxy cholecalciferol induces
synthesis of vitamin D-dependent Ca2+ binding
protein (Calbindin D-28K) in intestinal
epithelial cells.
 This mediates absorption of calcium
 Vitamin D deficiency impairs calcium
absorption and leads to deficiency.
 Causes rickets in children and osteomalacia in
adults.

33. 6.IRON
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 Absorbed into intestinal epithelial cells as free iron
or as heme (bound to Hb or myoglobin).
 The heme iron is converted to free iron.
 The free iron is then transported out of the
intestinal epithelial cells into blood by apoferritin
as ferritin.
 In the blood iron is transported by transferrin (a
βglobulin) to the liver storage sites.
 From the liver to the bone marrow to make
Hemoglobin.

34. INTESTINAL FLUID AND
ELECTROLYTE
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 9 Liters of fluid in GIT every day. (2L from diet
and 7L from GI secretions)
 Almost all reabsorbed with 100-200mls in
feces.
 Intestinal epithelial cells also secrete into the
GIT which also needs to be reabsorbed.
 Absorption is through cellular and paracellular
path
 Tight junctions are leaky in SI and tight in

35. Intestinal absorption
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 Isosmotic absorption like in the PCT of the
kidneys.
 Absorptive mechanisms vary in the jejunum,
ileum and colon.
 Jejunum: net absorption of NaHCO3
 Ileum: net absorption of NaCl
 Colon: net absorption of Na+ and K+

36. Jejunal absorption
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37. Ileum absorption
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39. Intestinal secretion
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 Cells lining the crypts secrete and those lining villi
absorb.
 The apical membrane has Cl- channels which are
closed but can be opened by hormones or NT’s.
 Ach & VIP activate adenyl cyclase>>>↑cAMP>
opening of Cl- channels
 Na+ follows Cl- and water follows them.
 If the secretion exceeds the absorption capacity
then a secretory diarrhea results as in Cholera.

40. DIARRHOEA
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 “TO RUN THROUGH”
 Fluid loss>> ↓ECF>> ↓intracellular volume>>
↓arterial pressure>> Baroreceptors and RAAS try
to compensate and if they fail>> circulatory
collapse.
 K+ loss: flow rate dependent and leads to
hypokalemia
 HCO3- loss: GI secretions have a high HCO3-
level

41. Causes of diarrhea
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 Decreased absorptive surface area: infection
or inflammation of small intestine, sprue
 Osmotic diarrhea : lactose intolerance.
Bacteria can compound this diarrhea by further
breaking lactose into more osmotic
compounds.
 Secretory diarrhea: in Cholera and Escherichia
coli infection.
 How does Cholera cause Diarrhea?

42. FECES FORMATION
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 Bacterial action in the colon:
 Cellulose digestion
 Vit K, B12, B1, B2
 Gasses (flatus): Carbon dioxide, hydrogen,
methane.
 Feces composition:
 ¾ water
 ¼ solid matter
 Brown colour: stercobilin, urobilin
 Odour: indole, skatole, mercaptans, hydrogen
sulphide

43. Thank you.
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