Histology Review Lectures 10/19 –
11/02/05
The immune and digestive systems
Myeloid and Lymphoid Immune
Systems
Myeloid: Granulocytes,
monocytes, RBC’s,
platelets.
Lymphoid: Lymphocytes
and associated organs
Bone Marrow
• Blood flows between marrow cords through
highly fenestrated blood sinuses instead of
capillaries.
• Reticular cells live between the fenestrated
endothelium and the marrow cells, are
important for secretion of CSF’s (colony
stimulating factors) and marrow structure
(reticular fibers-silver stain)
Hematopoiesis
• Embryonic:
– 1-3 mo. (gestation) Yolk sac blood islands
– 3-7 mo. Liver and spleen
– 7-9 mo. Bone Marrow
• Child: Most bones
• Adults: Most in the pelvis, sternum, ribs.
Hematopoiesis
• One type of cell, the pluripotent hematopoietic
stem cell, lives in the marrow and gives rise to
all blood cells, including some phagocytes,
such as Kupffer cells, histiocytes, osteoclasts,
etc.
• Remember! Osteoclasts arise from an early
stem cell; not a granulocyte or monocyte
progenitor cell.
• This pluripotent stem cell slowly differentiates
towards other cell types depending upon the
stimulating molecules present in the bone
marrow (GM-CSF, erythropoietin, etc.)
Erythropoiesis
• Proerythroblast: basophilic (ribosomes), large
nucleus, undergoes mitosis (m+)
• Basophilic Erythroblast: very basophilic (ribosomes),
smaller, m+
• Polychromatophilic Erythroblast: Hb begins, last cell
that is m+
• Normoblast: small, dark nucleus, slightly acidophilic
due to increased [Hb] (orthochromatophilic)
• Reticulocyte: lost its nucleus, acidophilic-gray
cytoplasm, many in bone marrow, also found in
blood of hemorrhaging patients to compensate.
(Polychromatophilic erythrocyte)
RBC
• 1. Erythrocyte: acidophilic, anuclear, biconcave
disc, 7-8 microns, 120d life span in blood.
– 1. Erythropoietin from kidney in response to hypoxia
causes more mitoses in erythrocyte precursors to give rise
to more RBC’s…
– 2. RBC’s are filled with mostly hemoglobin, use
glycolysis and pentose phosphate shunt to make ATP to
fuel enzymatic reactions. No mitochondria.
• Normal RBC count is 4-6 million/microliter blood (good for ECM
clinicals)
• Hereditary anemia- sickle cell, thalassemia, etc.
• Acquired anemia- decreased iron, B12, folate intake!!!
Granulopoiesis (similar for PMN,
Eos, Baso)
• 1. Myeloblast: no granules, basophilic, m+
• 2. Promyelocyte: azurophilic granules
appear here, indented nucleus, m+
• 3. Myelocyte: Elliptical nucleus, specific
granules appear here, last m+
• 4. Metamyelocyte: nucleus becomes more
indented, heterochromatic
• Band: nucleus acquires a U shape, these are
seen in blood with chronic infections.
Lymphopoiesis
• T-cells- originate in the bone marrow and
travel to the thymus in the youngster to
differentiate.
• B-cells – originate in the bone marrow, MALT,
spleen.
• Don’t really change appearance as they
mature.
Megakaryocytes
• 1. Megakaryoblast: last m+ cell, huge, basophilic
cytoplasm
• 2. Promegakaryocyte: really huge, 45 microns
• 3. Megakaryocyte: enormous, 50-70 microns,
polyploid, buds off platelets at platelet demarcation
channels in its peripheral cytoplasm. (proplatelet
processes)
The Lymphoid System
• Primary Lymph Organs
– Bone Marrow (B cells) and Thymus (T cells)
– Cells undergo antigen-independent proliferation,
differentiation. T and B cells are weeded out for their
ability to recognize foreign antigens (without actual
antigen present)
• Secondary Lymph Organs
– Lymph nodules, Lymph nodes, Tonsils, Spleen
– Cells undergo antigen-dependent prolif. and diff.
– Contain Lymphocytes (T and B), Macrophages,
Mesenchymal Reticular Cells (reticular fibers)
– T and B cells become effector lymphocytes and memory
cells.
Diffuse Lymphatic Tissue and
Lymphatic Nodules
• Diff. Lymph. Tissue: Accumulations of lymphocytes,
macrophages strategically placed along the gut and
respiratory tract. Interaction between antigen and
cells occurs here, then the B and T cells go to the
regional lymph nodes to differentiate.
• Lymph . Nodules: Localized uncapsulated
concentrations of lymphocytes. (Appendix, Peyers
Patches, Tonsils) Reactive lymphatic tissue, become
enlarged upon encounters with antigen. (Also found
in lymph nodes). Have a reticular stroma.
Lymph Nodes
• Small, Encapsulated organs along the pathway of
lymphatic vessels (filter lymph)
• Afferent lymph vessels supply it, efferent lymph
vessels drain it.
• Supporting structures
– Capsule - dense connective tissue surrounds the node
– Trabeculae – projections of the capsule into the cortex
– Reticular tissue – reticular cells and their fibers that form
a meshwork throughout the node
• Contain:
– Reticular cells
– B and T cells
– Macrophages (reticular macrophages)
Zones of the Lymph Node
• Cortex – Outer portion of the node
– Reticular framework, lymphocytes, macrophages, plasma
cells, lymph sinuses, lymph channels
– Lymph Nodules (follicles) – mostly B cells undergoing
mitosis from immunoblasts to plasma cells and memory
cells. Secondary nodules contain germinal centers.
– Deep cortex (paracortex) – mostly T cells, helping the B
cells, activating them, helping them recognize antigen.
• Medulla – Inner portion of the node
– Reticular framework, medullary cords and sinuses.
– Medullary cords – mostly B lymphocytes.
Lymphocytes enter
and exit the node
here
Spleen
• Morphologic and Immunologic blood filter
• Encapsulated with trabeculae, Contains Red
Pulp (Mostly RBC’s) and White Pulp (Mostly
lymphocytes, macrophages)
• No Cortex or Medulla.
• White Pulp contains:
– Peri-Arteriolar Lymphatic Sheath (PALS) – mostly
T cells
– Lymphatic Nodules – mostly B cells
• Lymph nodules, when reactive, can become very large
(Malphigian Corpuscles)
Spleen Functions
• Red Pulp:
– Contains Sinusoids that are highly fenestrated, and blood
comes in direct contact with endothelial-associated
macrophages. No continuous basal lamina, no pericytes or
smooth muscle in the sinusoids. RBC’s leave the sinuses
and enter the splenic cords (of Billroth), which are made of
reticular tissue, macrophages, some leukocytes. These
macrophages will be filled with hemosiderin from the
breakdown of senescent RBC’s.
• White Pulp:
– Contains lymphatic tissue, mostly involved in reactive
proliferation of lymphocytes and secretion of humoral
antibodies.
Thymus
• Arises from Endoderm – makes a reticular stroma –
no reticular cells, only epithelioreticular cells.
• The lymphocytes in the thymus come from the yolk
sac and then the bone marrow.
• T- lymphocytes are selected here; many undergo
apoptosis.
• Cortex stains dark, Medulla is eosinophilic, less
densely packed.
• Contains Hassal’s Corpuscles, with keratinized
epithelioreticular cells.
This is Reticulous!
• Remember which particular reticular tissue has which
cell!
– Epithelioreticular cells – Found in thymus
• Secrete “thymosin”, form blood/thymus barrier, Hassal’s Corps.
• NO RETICULAR FIBERS
– Reticular cells/ fibers
• Spleen – Cords of Billroth (with lymphocytes, et al.)
• Lymph nodes – Two kinds of Reticular Cells (APC’s, fibroblast-like
cells)
• Bone Marrow – (adventitial cells – support, secretes cytokines)
– Reticulocyte – immature RBC (lots of ribosomes)
The Digestive System
Lip
• External part: Keratinized. Hair follicles, sebaceous
glands, thin mucosa.
• Vermillion Border: Blood vessels in the dermis come
very close to the epithelium, skin appears red.
Keratinized. No hair follicles or sweat glands.
• Parakeratinized internal part: Just internal to the
vermillion border, some surface cells have nuclei,
some cells have keratohyalin granules.
• Mucosa: No keratohyalin granules, red connective
tissue shines through the thick yet transparent
epithelium.
External Part
Vermillion Border
Tongue
• Muscle- Skeletal, CN XII, random orientation.
• Papillae- mucosal elevations on the dorsum of the
tongue.
– Filiform – most numerous, smallest, keratinized, no taste
buds.
– Fungiform – on dorsum of tongue, mushroom shaped, have
taste buds.
– Circumvallate – found near the sulcus terminalis, have Von
Ebner’s glands and taste buds in their “moats”
– Foliate- found on the sides of the tongue, have taste buds.
Circumvallate
Von Ebner’s
Glands
Taste Buds
• Oval, pale bodies on papillae
• Cell types-
– Neuroepithelial cells – have microvilli, connect to
nerve fibers of CN VII, IX, X.
– Supporting cells
– Basal cells- differentiate into the above cells
• Buds at the tip of the tongue taste sweet
stimuli, back of the tongue taste bitter.
Major Salivary Glands
• Parotid: Found deep inside the cheek in front
of the ear. Totally serous acini. Many
adipocytes; do not confuse these with mucous
acini.
• Submandibular: Contains both serous and
mucous acini, found in the floor of the mouth
near the mandibular ramus.
• Sublingual: Totally mucous acini, found
underneath the tongue (surprisingly)
Salivary Gland
Ducts (ISE)
• Intercalated- low cuboidal, have
carbonic anhydrase (secrete
bicarb), most prominent in serous
glands.
• Striated- simple cubo/ columnar,
striations in the basal membrane-
elongated mito’s, central nuclei.
Reabsorb Na and Cl, add K and
HCO3. Creates Hypotonicity.
Intralobular.
• Excretory- Simple cuboidal to
stratified columnar, depending on
length. Interlobular!
Saliva and its
Ductal
modifications
Changes in [electrolytes] with changes in
flow rate.
Concentration (mM)
Flow (ml/min)
Saliva
• Contains:
– a-amylase (1-4 glycosidic bond breaker)
– Lysozyme (anti-bac), Immunoglobulin A
– Hi-HCO3, K, Ca. Low Na. (always hypotonic to
plasma)
• Sympathetics cause viscous saliva,
parasympathetics cause watery saliva.
Striated Duct
Intercalated Duct
Striated Duct
GI Tubing in General
GI Tubing in General
• Mucosa
– Epithelium (stratified squamous or simple columnar) – barrier,
absorption, secretion
– Lamina Propria – loose connective tissue, contains many blood vessels,
lymph vessels, immunologic barriers (lymphocytes, eos, mac), glands
– Muscularis Mucosae – boundary between muc and submuc, inner
circular and outer longitudinal smooth muscle
• Submucosa
– Dense, irregular CT, larger BV, lymphatics, nerve plexuses, sensory
and motor fibers, Glands in the duodenum and esophagus.
• Muscularis Externa (Propria)
– Inner circular and outer longitudinal layers of SM, Auerbach’s nerve
plexus
• Serosa
– Mesothelium and underlying Conn. Tissue. Retroperitoneal structures
have adventitial surrounding tissue.
Esophagus
Esophageal Glands
• Proper: SUBMUCOSA, more concentrated in the
upper ½ of esophagus. Mucus-secreting,
slightly acidic.
• Cardiac Glands: LAMINA PROPRIA, found at
extremities of the esophagus, usually next to
the stomach. Neutral mucus-secreting
(prevents against heartburn)
Esophageal Muscle
• Upper 1/3 – Striated (innervated by somatic
motor neurons)
• Middle 1/3 – a combination of upper and
lower
• Lower 1/3 – Smooth muscle (innervated by
vagus nerve (CN X)
Stomach
Features of the Stomach
• Mucosa
– Gastric Pit: made up of surface mucous cells, stain darker
than goblet cells, basal nucleus, secretes a thick alkaline
mucus, protective.
– Gastric Gland: connects to the gastric pit, contains:
• Mucous Neck Cells: shorter than surface cells, more soluble
secretion
• Parietal Cells: Large, clearer cells, secrete HCl and Intrinsic Factor
in response to gastrin
• APUD (enteroendocrine cells): do not contact the mucosa, secrete
gastrin and other hormones
• Chief Cells: secrete pepsinogen, which is converted to pepsin, a
protease, in the acidic lumen of the stomach.
Parietal Cell Electrolyte Transfer
Gastrin
Acetylcholine
Histamine
• Gastrin, Ach, Histamine activate this path.
• Somatostatin inhibits it.
Features of the Stomach
• Other Glands:
– Cardiac Glands: found in the upper stomach,
protects esophagus from acid. Connect to the
gastric pits.
– Pyloric Glands: found in the pyloric antrum and
the pylorus. Mucus secretion, located in lamina
propria.
• Muscularis Externa:
– Innermost oblique, middle circular, outer
longitudinal muscle layers.
• Rugae: folds of mucosa and submucosa
Small Intestine (Duodenum,
Jejunum, Ileum)
Small Intestine Characteristics
• Mucosa: Contains microvilli, villi (folding of
the mucosa), and plicae circularis (folding of
the submucosa). Three ways to increase
surface area.
• Cells of mucosa:
– Enterocytes (brush border, simple columnar.)
– Goblet cells (few microvilli, huge mucus cup)
– Paneth Cells (secrete lysozyme, found at bottom of
intestinal crypts of Lieberkuhn)
– APUD cells
Duodenum
• Submucosal
glands (of
Brunner)
• Secrete HCO3,
glycoproteins
• Regulates the pH
so that pancreatic
enzymes work!
Paneth Cells in Jejunum
Paneth vs. APUD cell
Trends in the Intestine
Duodenum Jejunum Ileum Colon
Goblet Cells 10% of all ~25% ~50% ~85%
epithelial
Plicae Start 5-6 Many at Become None
Circularis cm beyond beginning, less in (haustra)
pylorus, then taper number
most at off slightly and size
distal gradually
duodenum.
Lymph Few More More Yet Most
Nodules (Peyer’s)
Colon
Differences Between Colon and the
rest of the GI Tract
• The colon has a strong collagen table, a thickening of
collagen fibers just below the epithelium
• There are no villi, just crypts. No Paneth Cells
normally.
• The outer longitudinal layer of SM forms strong
bands (Taenia Coli) and is very sparse between them,
except in the rectum, where the outer layer is
confluent.
• There are no lacteals in the colon.
• A pericryptal fibroblast sheath in the lamina propria
secretes reticular fibers that line the epithelium.
Vermiform Appendix
Liver
Liver Function
• Detoxification of Blood
– Kupffer cells (phagocytosis), Enzymatic
degradation of drugs and toxins, Excretion of
metabolites into bile or urine.
• Carbohydrate and fat metabolism
– Gluconeogenesis, Glycogenolysis, Release of
glucose into blood, et al.
– Triglyceride, Cholesterol, Ketone synthesis
• Albumin, Plasma protein synthesis
• Bile Synthesis, conjugation of bilirubin.
Liver Acinus vs. Lobule
Liver Cells
• Hepatocytes
– Have junctional complexes, gap junctions
– Carry out all functions in the liver (metabolism, bile
synthesis)
– Have sER and rER, Microvilli, Bile canaliculi
• Kupffer Cell
– Liver macrophage, derives from monocyte
– Lives in the Space of Disse and in the Blood Space, clears
pathogens, lipoproteins, immune complexes
• Stellate (Ito) Cell
– Produces collagenase, metalloproteinase inhibitors,
become activated during cirrhosis.
• Endothelial Cell
– Highly Fenestrated, takes up blood components and
delivers them to the Space of Disse
The Space of Disse
Gall Bladder
Gall Bladder Features
• Stores and concentrates bile from the liver
– GB cells actively transport Na out of its
basolateral membrane, and water from bile
follows osmotically.
• Simple Columnar Epithelium
– Microvilli, junctional complexes, lateral plications
• No muscularis mucosae or submucosa.
• Rokitansky-Aschoff Sinuses – invaginations of
the epithelium where bacteria can grow
Pancreas
Exocrine Pancreas
• The pancreas secretes:
– Trypsinogen, Chymotrypsinogen, Proelastase,
Procarboxypeptdase, Prophospholipase, Procolipase –
these are zymogens.
– Trypsinogen is cleaved by intestinal enterokinase to
trypsin, and trypsin activates the rest.
– Also, lipase, amylase, cholesterolesterase, RNAse, DNAse
• These secretions mix with a bicarbonate-rich fluid
and enter the pancreatic duct and head for the
duodenum through the sphincter of Oddi.
• CCK stimulates the release of enzymes, Secretin
stimulates the intercalated duct system to release
more bicarb-rich fluid. Pancreatic Polypeptide
inhibits CCK at the acinar cell
Endocrine Pancreas
• The Islets of Langerhans are interspersed between
acini and are highly vascularized.
– Alpha cells- peripheral in the Islet, secrete glucagon.
(Raises blood sugar)
– Beta cells- central in the Islet, secrete insulin (Lowers
blood sugar, increases protein and fat synthesis,
glycogenesis)
– Delta cells- secrete somatostatin (inhibits both glucagon
and insulin, as well as gastrin, secretin, CCK)
– D1 cells- secrete VIP (like glucagon, but also affects the GI
tract tone and secretion
– F cells- secrete PP (inhibits bile secretion, stimulates
gastric enzyme secretion
– EC cells- secrete motilin, serotonin, subst. P (vasodilation,
increased gastric emptying)
Insulin
• A polypeptide hormone, derived by cleavage from
proinsulin to insulin and C-peptide.
• GLUT-2 Receptors in the beta cells take up glucose,
which signals the beta cell to manufacture and
secrete insulin. Amino acids and GI hormones also
can activate beta cells.
• Insulin is secreted into the bloodstream, where it
comes in contact with skeletal muscle or fat cells. The
insulin causes the GLUT-4 receptor to localize to the
membrane, increasing the amount of glucose that can
enter the cell.
• The insulin receptor is a tyrosine kinase that
autophosphorylates upon contact with insulin.
The cellular response to insulin
GLUT-4 activation
Panc. Duct
Islet
Paul Langerhans
Hormones secreted by pancreatic islet cells
Hormone Cell Hormone action
Beta
Insulin Lowers blood sugar
cell
Alpha
Glucagon Raises blood sugar
cell
Delta Inhibits insulin, glucagon, PP, and
Somatostatin
cell exocrine pancreas
Pancreatic Stimulates pepsin and HCl (acid)
F cell
polypeptide (PP) secretion by stomach
Islet amyloid Beta Inhibits glucose uptake by muscle (? role
polypeptide cell in Type 2 diabetes)
Acinar Cells
• ZG- zymogen
granule
• Asterisk-
lumen