Digestive System

Vagus nerve and motility
One function of the vagus nerve is to stimulate digestion by GI secretion and peristalsis throughout the digestive tract. The vagal nerve fiber myenteric plexus influences motility, and is strategically located between the circular and longitudinal muscle layers. The Meissners' plexus influence secretion and lies near the glandular regions.

Digestion and absorption

Micelle scheme by SuperManu

Carbohydrates are broken down to monosaccharides in the mouth, and are absorbed in the small intestine. intestine and pancreas. Intestinal and pancreatic glands secrete enzymes that also hydrolyze starches. (Different intestinal and pancreatic enzymes digest carbohydrate, protein and fat).

Protein digestion begins in the stomach and ends in the small intestine, where proteins are broken down to amino acids and small peptides.

Chylomicron illustration by OpenStax College

Fat is emulsified, or broken into small droplets, by the stomach. Triglycerides, cholesterol esters and phospholipids are broken down in the intestine, and then combine with bile salts to form micelles. Micelles carry the digested lipid products to be absorbed into the intestinal epithelial cell, where the triglycerides, cholesterol esters and phospholipids are reformed. These molecules are combined with apoproteins to form chylomicrons, which exit the cell into the lymphatics.

Chylomicrons travel to the liver, where by further processing, they become lipoprotein vehicles VLDL, LDL, IDL or HDL. Triglycerides are most concentrated in VLDL, which is transported to fat, skeletal and heart muscle cells. Cholesterol is found in all lipoprotein vehicles, but is most concentrated in LDL and HDL.

Table of digestive chemicals

Organ	Cell type	Produces	Function
Mouth	Salivary gland	Salivary amylase	Partially breaks down starch.
Stomach	Chief cell (Stimulated by gastrin, pepsin and HCl).	Pepsinogen	In the presence of acid, changes to pepsin and break down proteins to peptides.
	Parietal cell (Stimulated by vagus, gastrin, stomach stretch and presence of peptides. Inhibited by acidity, secretin, GIP, somatostatin and cholecystokinin).	HCl	Creates an acidic environment for pepsin, and has a small effect on starch hydrolysis.
		Intrinsic factor	Binds to vitamin B12 to aid its absorption in the small intestine.
	Gastrin cell (Stimulated by vagus, duodenum stretch and presence of peptides. Inhibited by acidity, secretin and GIP).	Gastrin	Stimulates parietal cell to secrete HCl, and increases intestinal motility.
Duodenum / Small intestine	Epithelial cells of Crypts of Lieberkuhn (Stimulated by vagus and direct contact with food. Secretin, GIP and cholecystokinin secretion are stimulated by fat and acid).	Maltase, Lactase, Sucrase	Splits maltose to glucose, lactose to glucose and galactose, and sucrose to glucose and fructose, respectively.
		Peptidase	Breaks down peptides to amino acids.
		Intestinal lipase, Intestinal enterase	Breaks down fats to glycerol and fatty acids, and cholesterol esters to free cholesterol and fatty acids, respectively.
		Secretin, Gastric inhibitory peptide (GIP), Cholecystokinin	Decrease gastrin secretion and motility.
		Enterokinase	A catalyst for the activation of pancreas peptides: trypsinogen, chymotrypsinogen, and procarboxypolypeptidase.
Pancreas (exocrine)	Exocrine cell (Stimulated by vagus, cholecystokinin and secretin).	Trypsinogen, Chymotrypsinogen, Procarboxypolypeptidase	Break down proteins to peptides and amino acids.
		Pancreatic lipase, Cholesterol esterase, Phospholipase	Breaks down triglycerides to fatty acids and monoglycerides, cholesterol esters to free cholesterol and fatty acids, and phospholipids to lysophospholids and fatty acids, respectively.
Pancreas (endocrine)	Beta islet cell	Insulin	Increases intestinal motility.
	Alpha islet cell	Glucagon	Decreases intestinal motility.
	Delta islet cell	Somatostatin	Decreases digestion and absorption, and insulin and glucagon secretion.
Liver	Liver cell	Bile salt	Emulsifies fat to smaller particles that can be digested by pancreatic enzymes.

Mechanoreceptors and Muscle Contraction

Sarcomere by Sameerb

A sarcomere is the interval between two Z discs. The series of interlocking actin and myosin filaments form a myofibril. Thousands of myofibrils form a muscle cell (muscle fiber).

Mechanoreceptors
Golgi tendon organs detect tension in muscle tendons. Muscle spindles lie within the center of a muscle, and detect stretch.

These receptors provide continuous feedback on the degree of muscle stretch and tension and the speed of stretching in order to achieve smooth and precise muscle action.

Muscle spindle
The two sensory receptors of muscle spindles are called primary and secondary nerve endings. They relay information about the degree of muscle stretching. Primary nerve endings also detect the rate of muscle stretching.

If a muscle remains stretched, the receptors send negative feedback information to the spinal cord and cerebellum, causing muscle contraction. If a muscle is suddenly stretched, then the primary receptors provide additional strong input to the spinal cord. An example is the knee jerk reflex.

Muscle spindles also consist of extrafusal muscle fibers (stimulated by gamma motor neurons), and smaller intrafusal muscle fibers (alpha motor neurons). Gamma motor neurons fire whenever alpha motor neurons fire, ensuring the length of intrafusal fibers and extrafusal fibers keep pace in contraction.

Golgi tendon organ
The Golgi tendon organ reacts against increased muscle tension by decreasing tension (allowing muscle to stretch).

Muscle contraction (animation)

1. An action potential spreads through the muscle fiber's T-tubules network. 
2. Depolarization of the muscle fiber eventually causes the sarcoplasmic reticulum to release calcium.
3. The calcium binds to the actin filament (on troponin C), causing an allosteric change of troponin and allowing tropomyosin to move. The binding site is unblocked. When calcium is present the blocked active site of the actin clears.
4. Myosin binds to the binding site on the thin filament, releasing phosphate and then ADP. (The myosin head has ADP and P_i attached in its high energy configuration). 
5. The release of ADP is coupled to the power stroke, where the myosin head pivots and pulls the actin filament toward the center.
6. ATP binds to myosin head, allowing it to release actin and be in the weak binding state. The lack of ATP results in the rigor state characteristic of rigor mortis.
7. ATP is split into ADP and P_i by hydrolysis.
8. Steps 4 to 7 repeat as long as ATP is available and calcium is freely found within the thin filaments.
9. Meanwhile, calcium is actively pumped back into the sarcoplasmic reticulum. When calcium is no longer present on the thin filament, the tropomyosin changes conformation back to its previous state, and blocks the binding site again. The myosin ceases binding to the thin filament, and the contractions cease. 

Neuronal Circuitry

Spatial summation
The postsynaptic neuron adds together the simultaneous firings of its presynaptic neurons until threshold. The axon hillock of the postsynaptic neuron then generates the action potential.

Temporal summation
The postsynaptic neuron receives rapid and frequent action potentials from few presynaptic neurons. Excited neurons have a greater effect on the postsynaptic neuron, causing the axon hillock to generate an action potential.

Neurotransmitters
Neurotransmitters that depolarize the postsynaptic neuron cause excitatory postsynaptic potentials (EPSPs). Neurotransmitters that inhibit the neuron from firing cause inhibitory postsynaptic potentials (IPSPs).

Acetylcholine, norepinephrine and glutamate are mostly excitatory. Dopamine, gamma-aminobutyric acid (GABA), glycine and serotonin are mostly inhibitory.

Neuronal circuitry

1. Convergence: a neuron takes in multiple inputs. 
2. Divergence: a neuron outputs to multiple cells. 
3. Negative feedback: neuron A stimulates neuron B that inhibits the outputs of neuron A. 
4. Lateral inhibition: a neuron stimulates its postsynaptic neurons, which send inhibitory signals and only a few excitatory signals. This limits neural impulses to a narrow path. 
5. Reverberation: a positive feedback circuit to sustain firing along a neural pathway. 

Blood Cells and Blood Clotting

Stimulus of RBC production

Decreased blood oxygen (anemia) stimulates erythropoietin production by the kidneys, a hormone that stimulates RBC production. 

Factors of RBC effectiveness

1. RBC production in the marrow. Radiation or drugs may suppress the marrow and decrease the number of RBCs. 
2. Iron in the diet to produce the hemoglobin molecule. An iron deficiency causes anemia. 
3. Vitamin B₁₂ and folic acid, important in the synthesis of DNA and the development of RBCs in the bone marrow. A deficiency of either will lead to megaloblastic anemia, where cells are large, fragile and short-lived.
4. Defects in the structure of hemoglobin may cause anemia. For example, sickle cell anemia. 
5. Defects in the red cell membrane. 
6. Defect in the metabolic pathway of RBCs. 
7. Immune reaction against RBCs, especially due to the cell defects above. 

Platelets

Platelets are small, anuclear cell fragments responsible for blood clotting. They secrete ADP and thromboxane A2 to activate other platelets to become "sticky". They also produce a fibrin-stabilizing factor that binds fibrin molecules to strengthen and form the clot, and prostaglandins that have various effects on blood flow and wound healing. They possess actin and myosin that allow them to retract and help close damaged blood vessel. The glycoprotein Von Willenbrand factor is the initial bridge that connects platelets to injured vessel wall. 

Blood clotting

1. Severed blood vessel causes local blood vessels to constrict. 
2. Extrinsic or Intrinsic pathway: 
• Extrinsic is a quick response triggered by tissue trauma releasing tissue thromboplastin. 
• Intrinsic is a slow reaction triggered by damage to RBCs, or by RBC contact with a foreign surface. 
3. Formation of prothrombin activator. 
4. Prothrombin activator catalyzes prothrombin to thrombin. 
5. Thrombin changes fibrinogen to fibrin threads that mix with RBCs, platelets and plasma to form a clot. 
6. Clot retraction and healing. 

Negative feedback mechanisms of blood clotting

• Fibrin absorbs excess thrombin, preventing the formation of more fibrin. 
• A globulin called anti-thrombin III inactivates excess thrombin. Heparin, produced by mast cells and basophils, is an anti-coagulant that works by enhancing anti-thrombin III activity. 
• Tissue plasminogen activator, released from damaged tissues, activates plasma protein plasminogen (profibrinolysin) to become plasmin (fibrinolysin). Plasmin lyses fibrin and helps remove the clot. 

Diseases of clotting

• Von Willenbrand's disease, caused by a defect in plasma adhesion and results in prolonged bleeding. 
• Hemophilia A and B are caused by missing Factor VIII and Factor IX, respectively. 
• Bleeding problems caused by vitamin K deficiency. Vitamin K is important in the formation of prothrombin and factors VII, IX and X. 

Respiratory System

Carbon dioxide in the body
CO₂ combines with water to form H₂CO₃ in the RBC, catalyzed by enzyme carbonic anhydrase. H⁺, from H₂CO₃, combines with hemoglobin (protein buffer) and HCO₃^- leaves the cell into plasma. When the RBC reaches the lungs, its hemoglobin releases H⁺ and H⁺ combines with a bicarbonate ion to reform CO₂.

Oxygen in the body

Unlike carbon dioxide, oxygen is not very soluble in plasma, but is carried on the hemoglobin of RBCs. In the oxygen-hemoglobin dissociation curve, hemoglobin easily gives up oxygen to tissues where there is low pO₂ (40 mmHg), yet binds well to oxygen in the alveoli where there is high pO₂ (60-100 mmHg). Hemoglobin also releases more O₂ when pCO₂ is elevated, when pH is low, or when temperature is high (where oxygen needs may be increased). This is represented by the dissociation curve shifting right, for reduced affinity.

How do cells control the use of oxygen?
The level of ADP limits O₂ consumption. This means when ADP is low (and there is abundant ATP), the cell doesn't need as much O₂. Less O₂ reacts in oxidative phosphorylation to produce ATP.

How does the brain control respiration? 
Carbon dioxide and H⁺
Increased blood CO₂ or H⁺ level stimulate the brain stem to increase respiration in order to remove excess CO₂ and decrease blood acidity. Carotid and aortic bodies are also stimulated to increase firing, which relays neural messages to the brain stem to increase respiration.

Oxygen
Decreased blood pO₂ increases the firing of the carotid and aortic bodies. This information is relayed to the brain stem.

Hering-Breuer reflex
Stretch in the lungs at the bronchiolar and bronchial tree tells the brain stem to inhibit inspiration.

Note: Remember that the CO₂ control mechanism also balances blood pH. The O₂ control mechanism is simple and does no more than balancing O₂ level.

Respiratory problems 
Inspiratory muscles / Control of respiration
Examples: brain stem injury, spinal cord injury, stroke, polio.

Pneumothorax
Air wrongly enters into pleural space, causing lung collapse due to inadequate negative pressure. Causes include obstruction of respiratory passage, thick membrane preventing efficient gas diffusion (pulmonary edema), fluid in alveolar space (pulmonary edema, pneumonia).

Diminished surface area of alveolar space from damage
Examples: collapsed alveoli (atelectasis), scarring of the lung (pulmonary fibrosis), alveolar destruction from smoking (emphysema).

Abnormally low blood oxygen (arterial hypoxemia)
Oxygen fails to diffuse into the lungs, due to low air ventilation or poor blood perfusion at the alveolar membrane.

Inefficient cardiovascular perfusion of tissues
Oxygen supply cannot meet the tissue energy needs during intense exercise.

Respiratory effort terminology

• Tidal Volume (TV), the average breath of air inhaled or exhaled.
• Inspiratory Reserve Volume (IRV), the extra amount of air that can be inhaled after TV.
• Expiratory Reserve Volume (ERV), the extra amount of air that can be exhaled after TV.
• Residual Volume (RV), the air left in lungs after strongest expiration.
• Functional Residual Capacity (FRC) = RV + ERV. (After TV exhalation, the total remaining volume of air in the lungs). 
• Inspiratory Capacity (IC) = TV + IRV. (After TV exhalation, the maximal volume of air that can be inhaled). 
• Vital Capacity (VC), the maximum amount of air you can ever inhale or exhale, an exchange between maximal intake and most forceful expiration.
• Total Lung Capacity (TLC), maximal volume of air in the lungs (after maximal inhalation).

Acid-Base Physiology

Hydrogen regulation
Depletion of chloride and K⁺ from the blood causes H⁺ loss

H⁺ is secreted into the renal tubule lumen, causing metabolic alkalosis. Specifically, chloride loss is accompanied by H⁺ to preserve charge (rather than Na⁺, which cannot accompany chloride in reabsorption). K⁺ loss decreases aldosterone release to allow more K⁺ into the blood. K⁺ is secreted into the plasma in exchange with H⁺ into the cell.

Sodium depletion of the blood causes H⁺ loss

Low Na⁺ causes more aldosterone to be secreted, and it stimulates potassium loss, which in turn stimulates H⁺ secretion in the same mechanism above. Another reason is that sodium depletion causes increased sodium reabsorption into the blood, where H⁺ exchanges for sodium during reabsorption and there is increased H⁺ secretion into the renal tubules. 

Buffering systems: HB ↔ H⁺ + B^- 

A common system involves a weak acid (HB), a strong acid (H⁺) and a weak conjugate base (B^-). The addition of a strong acid or base is partially neutralized by B^- or H⁺, and does not drastically change the pH.

1. Bicarbonate buffer: (CO₂ + H₂O) ↔ H₂CO₃ ↔ H⁺ + HCO₃^-
• The main extracellular buffering system. 
• Addition of a strong acid will shift the equation to the left, whereas strong base to the right. 
• To restore pH, the lungs may expire carbon dioxide and decrease blood acidity. The kidneys decrease blood acidity by secreting bicarbonate (which, in the acidotic state, is in lowered concentrations) to the blood, and excreting H⁺. 
2. Phosphate and ammonia buffers: H₂PO₄^- ↔ H⁺ + HPO₄^-2, NH₄⁺ ↔ H⁺ + NH₃
• Phosphate is an intracellular buffer, ammonia is an extracellular buffer. 
• Using these buffers, excess H⁺ can be neutralized and excreted as a weak acid. 
3. Protein buffer: H-protein (weak acid) ↔ H⁺ + protein (weak conjugate base)
• An intracellular buffering system. 

Respiratory acidosis 

May occur in advanced pulmonary disease, where lungs do not adequately remove carbon dioxide, and the blood becomes acidic. The kidney may compensate by reabsorbing more bicarbonate to the blood. 

Metabolic acidosis 

The addition of an acid to the body, other than carbonic acid, or the loss of bicarbonate from the body.  Bicarbonate is markedly decreased. The body responds by increasing respiration to remove carbon dioxide. 

Respiratory alkalosis

Too much carbon dioxide is removed by respiration. The kidneys compensate by excreting more bicarbonate. 

Metabolic alkalosis

An increase in plasma bicarbonate causes the body to decrease respiratory activity and preserve carbon dioxide. 

Electrolyte Balance

Kidney Nephron by Holly Fischer
Line divides cortex (light) and medulla (dark).

The kidney maintains the balance of electrolytes in the body. Its four functions include filtration, reabsorption, secretion and synthesis.

1. Filtration occurs at the glomerulus, where the negatively charged, sieve-like glomerular membrane filters out molecules that are large and negatively charged. 
2. Reabsorption occurs in the renal tubules (the majority at the proximal convoluted tubule). Nonpolar molecules are easily reabsorbed while ions are likely to be excreted. However, sodium is actively reabsorbed into the blood by co-transporters to power the transportation of other ions. 
3. Secretion occurs in the renal tubules, where unfiltered molecules in the blood may still be secreted into the tubular lumen to be excreted or reabsorbed. 
4. The kidney produces renin, bicarbonate, prostaglandin and erythropoietin, among other molecules. 

Loop of Henle, which direction?

Water reabsorption occurs in the descending limb. Think waterfall and water splashing out of the loop. Sodium reabsorption occurs in the ascending limb, which is also impermeable to water. This creates an interstitial environment that is "very salty" or hyperosmolar, and where water permeability is increased by ADH. Therefore, ADH enables water to leave the collecting ducts and concentrates urine. 

Regulation of sodium

Ingestion

The hypothalamus induces "thirst" if sodium concentration is high. 

Excretion

There are two autoregulatory processes. In glomerular-tubular balance, the glomerular filtration rate (GFR) influences how much sodium is filtered, and therefore, how much of (the same amount of) sodium is reabsorbed. In tubulo-glomerular feedback, the macula densa senses excessive fluid flow, which is reflected in increased GFR, and constricts the afferent arterioles to decrease GFR. 

Hormone atrial natriuretic factor (ANF) responds to excessive blood volume and cardiac atria dilation, and induces sodium excretion. ADH responds to increased sodium concentrations in the blood, and conserves water to restore normal serum osmolality. 

To avoid charge buildup, sodium cations must be transported with an anion, or be exchanged with a cation, such as K⁺ or H⁺. Examples: in the late proximal tubule, Na⁺ is reabsorbed with Cl^-; in the ascending loop of Henle, the Na⁺-K⁺-2Cl^- cotransporter reabsorbs these ions into the cell. 

Collecting duct by Lennert B (edited)

Regulation of potassium

Potassium is the main intracellular cation, and the Na⁺/K⁺-ATPase pump keeps potassium in cells. Aldosterone stimulates the pump to take K⁺ into the cell and Na⁺ into the blood. In times of low plasma sodium, low blood pressure or high plasma potassium, aldosterone facilitates Na⁺ into the tubule cells (and into the blood via Na⁺/K⁺-ATPase) while K⁺ is excreted.

pH change
When blood pH decreases (and [H⁺] increases) H⁺ tends to enter cells in exchange for K⁺. When pH increases H⁺ tends to leave cells in exchange for K⁺.

Regulation of chloride
The most common extracellular anion, and is exchanged with anion bicarbonate or is carried with sodium.

Circulatory Control

Autoregulation
The brain, heart and skeletal muscle exhibit autoregulatory control over their blood vessels (as opposed to blood vessels of organs under sympathetic nerve innervation). This control is based on the metabolism of surrounding tissues, and regulates blood flow locally; If there are factors such as carbon dioxide, lactic acid or certain ions, then the blood vessels will dilate. Conversely, excess blood flow will trigger vasoconstriction.

Regulation by the nervous system
Brain stem
The brain stem fires sympathetic nerve messages, and the sympathetic nerves release norepinephrine only. Sympathetic nerves also stimulate the adrenal medulla to secrete epinephrine and norepinephrine. The overall effects are raised blood pressure and increased heart rate in response to blood pressure changes.

Receptor	Response to	Location	Effect
alpha-1	epinephrine and norepinephrine	peripheral blood vessels	vasoconstriction
beta-1	norepinephrine and sympathetic nerves	heart muscle	increase cardiac output
alpha-2	norepinephrine	presynaptic terminals of CNS	negative feedback inhibiting norepinephrine release
beta-2	epinephrine	blood vessels of the skeletal muscle and heart	vasodilation

Hypothalamus
The hypothalamus releases ADH, which increases water reabsorption in kidneys and also constricts peripheral blood vessels.

How are changes in blood pressure detected?

1. If blood pressure is too high, baroceptors in the carotid and aortic sinuses (vessels in the upper body) fire signals that inhibit sympathetic output. 
2. The hypothalamus responds to increased serum osmolality (mainly increases of sodium in the blood) by secreting more ADH. 
3. The brain stem responds to increased concentrations of blood CO₂ and H⁺, which are associated with low blood pressure and poor blood flow, by stimulating sympathetic output. 

Regulation by the kidney

Glomerular level

Water filtration at the glomerulus depends on the hydraulic pressure and osmotic pressure of blood.  The higher the hydraulic pressure, the more easily blood will pass through filtration to be secreted. The higher the osmotic pressure, the more amount of water in the blood that can be filtered. 

During filtration, plasma osmolality is higher in the vessels because blood is more concentrated with proteins that do not pass into the nephron. Water tends to be drawn back into the blood due to osmotic pressure (to reach equilibrium). Thus, one must consider osmotic pressure with hydraulic pressure to determine how much water is filtered. 

ADH and angiotensin II (from the renin pathway) stimulate mesangial cells in the glomerular capsule to contract. This decreases surface area and membrane permeability and more water is retained. 

Renal corpuscle by M.Komorniczak

A: Renal corpuscle. B: Proximal tubule.
C: Distal convoluted tubule. D: Juxtaglomerular apparatus.
5: Mesangium 6: Granular cells. 7: Macula densa.
(Note the location in the nephron, upper left diagram). 

Juxtaglomerular apparatus and renin-angiotensin-aldosterone pathway

Three ways to stimulate renin secretion:

1. Granular cells of the juxtaglomerular apparatus secrete renin in response to sympathetic stimulation. 
2. Granular cells secrete renin directly in response to low blood pressure. 
3. If renal tubular fluid is low in sodium, the macula densa stimulates granular cells to secrete renin. Low sodium in the renal tubules is typically the result low blood volume and slow fluid filtration, which allows too much sodium to be reabsorbed into the blood as filtrate moves too slowly. 

Renin converts angiotensin (produced by the liver) to angiotensin I. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, which stimulates the adrenal cortex to secrete aldosterone. Aldosterone promotes reabsorption of sodium into the blood, thereby increasing blood volume and pressure. Remember water follows ions. 

Regulation by the heart

Atrial natriuretic factor (ANF)

Stretching of the atrial walls (by increased blood volume) releases ANF, which promotes sodium secretion and therefore loss of water. This results in lower blood volume and pressure. 

Sterling's Law

Greater cardiac stretch or stroke volume = greater cardiac contraction, an automatic response to match heart input and output. 

Autoregulation 

See top. 

Blood Pressure and Flow

Systolic/Diastolic
Blood pressure is written as the pressure in the brachial artery as the ventricles contract (systolic) over the pressure when the ventricles relax (diastolic).

Pressure difference drives blood flow
BP is highest in the arteries, and is lowest in the veins. The pressure drop is caused by resistance as blood passes from the arteries through the capillaries. The difference in pressure is what drives blood flow (perfusion).

Factors of blood pressure 
BP is controlled by volume and flow resistance. If blood volume increases, so does cardiac output (L/min) and BP. Peripheral resistance can be caused by increased blood viscosity or vasoconstriction in the arteriolar level; the resulting backup of blood in the arteries causes BP to increase.

Sympathetic nerve innervation causes vasoconstriction in blood vessels (of certain organs) with vasoconstrictive receptors.

Factors of blood flow
Of the heart:
Cardiac output is influenced by contractile force, heart rate, and venous return to the heart. Increased venous return is dependent on increased: blood volume, dilation of arteries, differential pressure between arteries and veins, skeletal muscle contractions which move blood along veins.

Of the peripheral tissues:
Increased flow is dependent on increased: cardiac output (except in coronary arteries which feed to heart muscle - a systole also contracts these arteries, blocking some flow), blood volume, vessel dilation, time spent lying down.

Also see the Poiseuille equation for factors affecting flow (Q), noting what is directly or inversely proportional to Q.

Mycoplasma

Mycoplasmatacae are the tiniest free-living organisms capable of replicating. They are unique bacteria because they lack cell walls, having only cell membrane with sterols for protection from the environment. The lack of a cell wall explains why penicillin and other antibiotics do not attack mycoplasmatacae. Two pathogenic species are Mycoplasma pneumoniae and Ureaplasma urealyticum.

Mycoplasma pneumoniae 
It is the leading cause of bronchitis and pneumonia in young adults. The mild symptoms of gradual fever, sore throat and cough is called walking pneumonia. However, it is unknown why 7% of infected patients develop severe symptoms of erythema multiforme or Stevens-Johnson syndrome.

Ureaplasma urealyticum 
Found in urine and breaks down urea. It is part of normal flora in 60% of sexually active women. It can infect the lower urinary tract, causing non-gonococcal urethritis.

Mycobacteria

These bacteria are rods that have high lipid content in their cell walls, which makes them acid-fast on staining. (Red stain is applied and heated to penetrate bacteria, acid alcohol is poured over the smear, then a counter stain methylene blue is applied). Mycobacteria are stained red as their cell walls do not wash off with acid alcohol, thereby retaining the first stain. Mycobacteria and Nocardia are two major acid-fast organisms.

Mycobacterium tuberculosis 
Commonly infects the lungs, causing the chronic disease tuberculosis. These bacteria possess mycosides, lipids that are only present in acid-fast organisms, which are involved in virulence. The formula of a mycoside is a mycolic acid bound to a carbohydrate.

• Mycosides: 
• Cord factor - formed by two mycolic acids and a disaccharide. 
• Sulfatide - like cord factors, but sulfates are attached to the disaccharide. 
• Wax D - complex mycoside that activates the immune system. 
• Stages of tuberculosis: 
• In primary tuberculosis, inhaled bacteria infect the lung, but is usually asymptomatic. Bacteria enter macrophages and then lymphatics and other areas of the body. Cell-mediated immunity will suppress the bacteria, but they can cause secondary tuberculosis.  
• Secondary or reactivation tuberculosis occurs after the bacteria lie dormant. Infection can occur in any organ. 

Mycobacterium leprae 

An acid-fast, rod bacterium. Causes leprosy as it grows on the skin, preferring cooler body temperatures. This is why warm areas such as the armpit and groin are spared. Disease severity depends on one's immune system. 

• Diseases:
• Lepromatous leprosy (LL), where the lack of cell-mediated immune response in patients causes leprosy in its the severest form. The reason may be due to defective T-suppressor cells that block Th cell response to the bacteria. 
• Tuberculoid leprosy (TL), a milder form of leprosy as there is cell-mediated immune response against the bacteria. 

Spirochetes (Gram-Negative)

Treponema pallidum

Spirochetes are tiny gram-negative bacteria that resemble corkscrews. This is a unique group because spirochetes have an additional phospholipid-rich membrane, and periplasmic flagella, which protrude sideways from the cell wall under the outer membrane. Spirochetes are divided into Treponema, Borrelia and Leptospira.

Treponemes do not produce toxins or tissue destructive enzymes. Instead, disease is caused by autoimmune responses.

Treponema pallidum
Causes the STD syphilis. Transmitted by contact with open skin or vaginal, anal or oral sex.

• Stages of syphilis:
1. Painless ulcer and painless regional swelling of lymph nodes. 
2. Rash on palms and soles. Condyloma latum, painless bumps on genitals. Almost any organ can be infected, resulting in fever, weight loss and lymphadenopathy (abnormal lymph node size). 
3. Most patients recover from the symptoms of the secondary stage, but 25% will relapse and develop the symptoms again. 
4. Slow inflammatory damage to organs, blood vessels and nerve cells. Patients either exhibit: Gummas (lesions of the skin and bone); Cardiovascular syphilis (aneurism of the aorta as the media layer becomes necrotic); Neurosyphilis (subacute syphilis, meningovascular syphilis where blood vessels of the brain is infected, tabes dorsalis damaging the spinal cord, general paresis leading to mental deterioration, or asymptomatic).  
• Congenital syphilis:
• Early congenital - symptoms resemble adult secondary syphilis. 
• Late congenital - similar to adult tertiary syphilis except heart damage is rare. 
• Subspecies:
• Endemicum causes skin lesions that are mostly oral. Gummas of the skin and bone may develop. 
• Pertenue causes the disease yaws. Papules and lesions appear on the skin, and later tertiary gummas develop in the skin and bones. 
• Carateum causes the disease pinta. Papules develop, followed by lesions on the skin that turn blue in the sun. 

Borrelia burgdorferi 
Causes lyme disease, transmitted by insects.

• Stages of lyme disease:
1. Early localized - a skin lesion at the site of tick bite, called erythema chronicum migrans (ECM). It is a rash that spreads out over time. 
2. Early disseminated - smaller, multiple ECM on the body. Four organs can be invaded: 
• Brain and nerves: meningitis, cranial nerve palsies (especially Bell's palsy), and peripheral neuropathies. 
• Heart: transient heart blocks and less commonly, myocarditis. 
• Joint: brief attacks of arthritis. 
3. Late - chronic arthritis or chronic neurologic damage. 

Borrelia recurrentis
Transmitted to humans by body lice. The bacteria spreads in the blood, causing a high fever, headaches and muscle aches. Symptoms relapse due to antigenic variation of surface proteins exhibited by the bacteria.

Leptospira
Transmitted to humans who come in contact with animal urine. In the first phase of disease: high spiking fever, headache and severe muscle aches, and red eyelids. In the second, immune phase: meningitis.

Leptospira interrogans can cause the more severe Weil's disease, or infectious jaundice. It causes renal failure, hepatitis, jaundice and hemorrhages in many organs.

Chlamydia and Rickettsia (Gram-Negative)

These bacteria are obligate intracellular parasites, meaning they can only survive inside animal cells. Chlamydia and rickettsia resemble viruses because of their size and parasitism. Unlike viruses, they can synthesize their own proteins, posses both RNA and DNA, and are sensitive to antibiotics. Chlamydia spreads from person to person, and rickettsia spreads from arthropod to person.

Chlamydia life cycle 
The bacterium has a dense, small, inert form called the elementary body (EB). It is spread from cell to cell in the host, and becomes an initial body (IB), or reticulate body. IBs replicate before some are transformed back to EBs, which infect more cells.

Chlamydia trachomatis 
Primarily infects the eyes and genitals, and causes STD.

• Diseases: 
• Trachoma, a type of chronic pink eye (conjunctivitis) and causes preventable blindness in the course of 10-15 years.
• Inclusion conjunctivitis of newborns by infection from the birth canal. Causes swelling, inflammation and pus.
• Infant pneumonia. 
• Urethritis. As Neisseria gonorrhoeae most commonly causes urethritis, the disease caused by other bacteria is labeled nongonococcal urethritis (NGU). 
• Cervicitis. 
• Pelvic inflammatory disease (PID).
• Epididymitis, which can develop in men with urethritis. 
• Lymphogranuloma venereum, an STD that exhibits painless bumps or ulceration on the genitals. Once bacteria migrate to the lymph nodes, the nodes swell and may break open.

Chlamydia psittaci
Infection is transferred from birds to humans. This bacteria common causes an atypical pneumonia called psittacosis.

Rickettsia rickettsii
Transmitted to humans by ticks. Bacteria proliferate in the blood vessel and capillary endothelium, and cause Rocky Mountain spotted fever. The skin rash of the disease is caused by small hemorrhages and inflammation.

Rickettsia akari
Transmitted to humans by mites. Causes rickettsialpox, which starts with a localized red bump on the bitten skin. The bump turns into a blister. Later, fever and headache develop and pox covers the body.

Rickettsia prowazekii 
Causes epidemic typhus, especially in places of overcrowding, poverty and unsanitary conditions. (Epidemic is widespread and sudden. Endemic affects a population for a consistent time). Disease is transmitted by lice. Symptoms include fever, headache and small pustules on the skin. Unlike Rocky Mountain spotted fever, there is no rash on the palms, soles or face.

Rickettsia typhi
The endemic form of typhus, murine typhus, but symptoms are not as severe. Transmitted by fleas.

Rickettsia tsutsugamushi
Transmitted to humans by mite larvae. Causes scrub typhus.

Rickettsia parkeri
Infection started in the southeast coast of the US. Symptoms include fever, headache, eschar (scab) and regional lymphadenopathy (abnormal lymph node size). 

Rickettsia africae
Causes African tick-bite fever (ATBF).