BMS 310 FINAL
Module 8: Respiratory system
Asthma
Upper respiratory tract- nasal cavity, pharynx, larynx
Lower respiratory tract- trachea, carina, primary bronchi, bronchioles, alveoli
Compliance: measure of lung and chest wall distensibility
Increased compliance- lungs are easy to inflate, lost some elastic recoil
Decreased compliance- lungs are abnormally stiff and difficult to inflate
Pousille’s law: flow rate decreases and resistance increases
Stimulation of sympathetic β₂ adrenergic receptors causes bronchodilation
Stimulation of parasympathetic receptors causes bronchoconstriction
Symptoms associated with asthma:
Wheezing
Cough
Status asthmaticus: symptoms cannot be reversed, can be fatal
Symptoms during an episode of asthma:
Narrowed airway
Bronchospasm
Mucosal edema
Secretion of viscous mucous
β₂ adrenergic receptor agonist mechanism of action: stimulate the sympathetic nervous system. Epinephrine and related compounds bind to β₂ adrenergic receptors promoting smooth muscle relaxation and bronchodilation
Cholinergic receptor antagonist mechanism of action: Inhibit the parasympathetic system. Block cholinergic muscarinic receptors causing bronchodilation.
Phosphodiesterase inhibitors mechanism of action: Inhibits phosphodiesterase enzymes, which increases cAMP levels, promoting bronchodilation
Intal (cromolyn sodium, mast cell stabilizer) mechanism of action: Blocks mast cell activation, decreasing immune response and release of histamine.
Corticosteroids mechanism of action: Inhibits mast cells and immune cells from making cytokines, decreasing airway inflammation.
Singulair (monteleukast), Accolate (zafirlukast), zyflo (zileuton) mechanism of action: Block leukotriene formation.
Omalizumab (Xolair) mechanism of action: Stops IgE formation.
COPD
Chronic cigarette smoking causes chronic irritation and breakdown of elastin
Link between COPD and heart failure
Shunted blood→ compensatory hypertrophy→ creates V/Q mismatch
NORMAL VALUES
Alveolar ventilation (Va)= 4L/min
Pulmonary capillary perfusion (Qc)= 5L/min
V/Q match = 0.8
Decreased alveolar ventilation = decreased V/Q ratio
Decreased pulmonary capillary perfusion = increased V/Q ratio
Shunting of blood: blood leaves the lungs the same way it entered (deoxygenated)
Reaction of pulmonary arterioles supplying blood to poorly ventilated alveoli
Decreased oxygen to diffuse into blood, leads to decreased oxygen carrying capacity of blood which causes hypoxemia and hypoxia
BV reflex occurs- pulmonary artery undergoes vasoconstriction, an attempt to divert blood to ventilated alveoli
R. ventricle has increased workload→ compensatory hypertrophy→ r. sided heart failure
Chronic bronchitis: Chronic productive cough (3 months of the year for 2 years). Inspired irritants result in irritation and infiltration of neutrophils, macrophages, and lymphocytes which produce exudate.
Associated airway changes:
Chronic productive cough
Mucous glands hypertrophy
Increased goblet cells
Impaired cilia
Cor pulmonale: right sided heart failure due to a primary pulmonary pathology
Systemic complications:
Edema, distended jugular, abdominal ascites, enlarged viscera
Emphysema: Abnormal permanent enlargement of gas exchange airways by destruction of alveolar walls.
Affects lobules
Centrilobular: Affects respiratory bronchioles. Elastic breakdown due to increased protease activity and deficiency of 𝛼-1-antitrypsin.
Panlobular: Affects the entire lobule. Associated with long term smoking or genetic mutation of 𝛼-1-antitrypsin.
Incentive spirometry is used to measure airway resistance upon complete exhalation.
Increased resistance = decreased FEV/FVC ratio
COPD treatment: inhaler (steroidal), oral steroids, bronchodilators
Restrictive Diseases
Acute Respiratory Distress Syndrome (ARDS)
Direct injury to lungs→ type II pneumocyte damage & endothelial damage, causing inflammation→ decreased surfactant production, atelectasis, decreased compliance, alveolocapillary membrane permeability, pulmonary edema, pulmonary hypertension, V/Q mismatch→ right to left shunt, hyaline membrane formation, fibrosis
Hyaline membranes form due to deposition of fibrin and infiltration of neutrophils and macrophages, cellular debris and red blood cells that line and fill alveolar spaces.
Blocks gas exchange and perfusion
Caused by exudate
Infant Respiratory Distress Syndrome: Underdeveloped lungs don’t produce surfactant, alveoli collapse upon exhalation, causing atelectasis and hypoxemia
Symptoms: cyanosis, harsh breath sounds, flared nostrils, pooling of blood, peripheral edema
Treatments: CPAP, surfactant replacement therapy
Pneumoconiosis: Any change in the lungs caused by inhalation of inorganic particles
Chronic inflammation, scarring of alveolocapillary membrane
Berylliosis: due to inhaled beryllium
Treatments: corticosteroids, immunosuppressants, lung transplant
Silicosis: due to inhaled silica dust
Causes pulmonary nodules and fibrotic interstitial infiltrates
Treatments: reduce exposure, cough medicine, bronchodilators
Anthracosis: due to inhaled carbon particles.
Causes black discoloration of lungs
Often asymptomatic
Asbestosis: due to inhaled asbestos
Causes fibrosis
Pneumonia: Infection of the lower respiratory tract caused by bacteria, virus, fungi, protozoa, parasites
Age group with highest mortality- children under 5 and adults over 65
Pathophysiology: accumulation of secretions, mucociliary elevator impairment (mucus remains stagnant), alveolar macrophage impairment, pulmonary congestion
Bronchopneumonia: spots of fluid accumulation, earlier stages
Lobar Pneumonia: Accumulation of fluid in entire lung, later stages
Red hepatization: Early on there is more blood flow and red fluid; associated with bronchopneumonia
Grey hepatization: Later on there’s more protein-rich exudate and non-red fluid; associated with lobar pneumonia
Module 9: Renal System
~1.2 million nephrons within each kidney
Glomerular filtration membrane
Podocyte filtration slits
Basement membrane
Contains proteins
Heparin sulfate proteoglycan- maintains negative charge
Collagen type IV- soluble
Endothelial fenestrations
NORMAL LAB VALUES
Blood urea nitrogen (BUN)- 9-25 mg/dL
Creatinine- 1 mg/dL
Cystatine type C- 1 mg/L
Increased values within plasma = decreased renal function
Erythropoietin is produced in response to decreased oxygen. Stimulates RBC production
Renin is released in response to decreased blood pressure and renal perfusion. Leads to formation of angiotensin II which raises blood pressure and causes vasoconstriction and aldosterone-mediated salt retention.
Glomerulonephritis
Causes of renal failure
Pre-renal- pathology before blood enters kidney
Intra-renal- pathology is intrinsic to kidney
Post-renal- pathology is upon blood exiting the kidney
Nephrotic syndrome: altered glomerular permeability and loss of negative charge
Associated with glomerulonephritis
Patient would present with peripheral edema
Increased filtration of plasma proteins→ proteinuria→ hypoalbuminuria→ decreased oncotic pressure in blood vessels→ fluid leaks into interstitial spaces
Affects 4 systems
Cardiovascular- hypoalbuminuria
Skeletal- decreased vit D
Endocrine- decreased thyroxine
Immune- decreased immunoglobulins
Glomerular lesions
Diffuse- uniform involvement of most/all glomeruli
Focal- changes in some glomeruli (>50%)
Mesangial- deposition of immunoglobulins in mesangial matrix
Membranous- thickening of glomerular capillary wall with immune deposits
Mesangial cells: secrete mesangial matrix and support glomerular capillaries
Involvement with proliferative glomerulonephritis- Mesangial cells are the most susceptible to proliferation. When matrix is deposited between cells it causes increased permeability and decreased selectivity
Type III hypersensitivity reactions/ Acute proliferative glomerulonephritis
Immune complexes in patchy deposition
Decreased selectivity and increased permeability
Proteinuria and hematuria
Mesangial cell proliferation → decreased lumen diameter, increased resistance, decreased blood flow and decreased filtration rate, increased waste products in blood
Kidney senses decreased filtrate→ renin is released→ formation of angiotensin II→ increased blood pressure
Type II hypersensitivity reactions/ Acute membranous glomerulonephritis
Linear deposition of immune-complex
Chronic glomerulonephritis: chronic glomerular injury by circulating immune complex
Long duration and irreversible
Immune complex made in a small amount of long period of time
Low levels on protein in urine over long period
Increased permeability, decreased function
Acute and Chronic Renal Failure
Glomerulosclerosis
Diffuse glomerulosclerosis: can cause nephrotic syndrome and/or renal failure with or without hypertension
Symptoms- edema, albuminuria, waxy casts
Nodular glomerulosclerosis: mild or no nephrotic syndrome. Rarely causes symptoms.
Kidney pathology and hypertension
Kidney detects decreased renal perfusion, blood flow, filtration, and filtrate volume and flow
Renin is released, causing the formation of angiotensin II→ vasoconstriction and hypertension
Diabetic nephropathy: uncontrolled hyperglycemia→ nephroangiosclerosis→ decreased lumen and GFR
Over time decreased blood flow causes hypoxic medulla, cells under necrosis
Necrosis of papilla- necrotizing papillitis
Acute Kidney Injury (AKI): Destruction of tubule epithelial cells and sudden suppression of kidney function
Serum creatinine levels are used to stage AKI
Stage 1- increased SCr by 50% in 7 days
Stage 2- increased SCr by 2.0-2.9 x baseline within 48 hrs
Stage 3- increased SCr by 3.0 x baseline within 48 hrs OR increased SCr by >4.0 mg/dL
Causes of acute renal failure
Prerenal (functional)- hypotension, Na loss, hepatorenal syndrome, inadequate kidney perfusion
Intrarenal (structural)- acute tubular necrosis, acute severe glomerulonephritis
Postrenal (obstructive)- kidney stone
Recovery possible
Acute tubular necrosis
Initiation Phase- injurious stimuli creates damage
Decreased blood flow, urine volume, filtration & secretion
Maintenance Phase
Decreased blood flow, urine volume, filtration & secretion
Hyperkalemia and hypervolemia
Recovery Phase
Urine production restarted, increased blood flow, filtration & secretion
Hypokalemia and hypovolemia
Osmotic diuresis: excessive water loss due to immature cells
Recovery from acute renal failure is possible
Five Stages of Chronic Kidney Disease
Stage 1- no change in function of symptoms, hypertension is common
GFR >90 mL/min
Stage 2- mild kidney damage, hypertension
GFR 60-89 mL/min
Stage 3- moderate kidney damage, hypertension, increased urea and creatinine levels
GFR 30-59 mL/min
Stage 4- severe kidney damage
GFR 15-29 mL/min
Stage 5- end stage kidney
GFR <15 mL/min
Intact Nephron Hypothesis: intact nephrons undergo compensatory expansion of filtration, reabsorption, and secretion
Eventually all nephrons undergo necrosis
Module 10: Gastrointestinal
Four layers of GI tract
Serosa: connective tissue layer, peritoneum, above subserosal plexus
Muscularis: longitudinal and circular muscle layers
Myenteric plexus beneath longitudinal layer
Submucosal plexus beneath circular layer
Submucosa: glands, ducts
Mucosa: mucous epithelium, lamina propria, muscularis mucosae
Eight Digestive Processes
Ingestion, chemical digestion, mechanical digestion, secretion, absorption, elimination, immune protection, propulsion
Achalasia: inhibitory neurons in myenteric plexus degenerate causing smooth muscle atrophy within middle and lower esophagus.
Symptoms- trouble swallowing, aperistalsis, incomplete relaxation of lower esophageal sphincter, increased resting tone of lower esophageal sphincter
Treatment-
Medication (oral and injections)- nitroglycerine, Ca channel blockers
Surgical- myotomy
Mechanical dilation- balloon
Sliding Hiatal Hernia: Stomach pushes through diaphragm at esophageal hiatus; most common
Paraesophageal Hiatal Hernia: stomach pushes through diaphragm at opening near esophagus
Surgical emergency- causes congestion of mucosal blood flow, gastritis, ulcers
Chief cells: secrete pepsinogen, precursor to pepsin
Parietal cells: secretes HCl, intrinsic factor, gastroferrin
Mucous cells: secretes alkaline mucus, prostaglandins, HCO3
Gastritis: nonspecific inflammation of gastric mucosa
Acute gastritis: caused by injury of protective mucosal barrier
Risk factors- NSAIDs, smoking, alcohol, stress, shock
Treatment- usually heals spontaneously within a few days; healing can be facilitated by antacids, and H2 receptor antagonists or proton pump inhibitors
Chronic gastritis: 10%, recessive, multi genetic, fundal
Type A: loss of T cell tolerance and development of antibodies to parietal cells
Achlorhydria- stomach doesn't produce HCl
Can cause pernicious anemia due to malabsorption of vit B12
Type B: 90%, antral
Caused by chronic alcohol, tobacco, or NSAID use; or by H. pylori bacteria
High levels of HCl, increased risk of duodenal ulcers
Peptic ulcer: ulceration of protective mucosal epithelium
Common causes- NSAIDs (aspirin!), alcohol, oversecretion of HCl, H. pylori infection
Aspirin inhibits prostaglandin synthesis by inhibiting COX-1 enzyme
Stomach cancer
Risk factors- smoking, alcohol, H. pylori infection, nitrates, salt, chronic gastritis
Symptoms- weight loss, loss of appetite, bleeding, indigestion, vomiting, bleeding
Intestines
Celiac disease/ gluten-sensitive enteropathy: autoimmune disease that damages small intestinal villous epithelium where gluten is ingested
Related to human leukocyte antigens (HLA-DQ2 and HLA-DQ8)
Causative factors- early infections, infant gut microbiota, timing and amount of gluten ingested
Leaky gut syndrome- intestinal mucosa becomes more permeable allowing bacteria, toxins and others into blood
Larazotide: when taken before eating reduce inflammation
Maintains and restores tight junctions by blocking zonulin receptors
Nexvax2: vaccine to re-educate immune system by gradual exposure to specific gluten peptides/epitopes
Schilling test: intrinsic factor and B12 eaten at the same time, if B12 is in urine when taken with IF then there is no intestinal disorder
Ulcerative colitis: chronic inflammatory disease that causes ulceration of colonic mucosa of rectum and sigmoid colon
Pathophysiology- decreased mucin secretion→ increased permeability of mucosa→ increased passage of pathogens→ increased stimulation of gut immune system with inflammatory response
Clinical manifestations- periods of remission and exacerbation
Complications- anal fissures, diarrhea, urgency, hemorrhoids, perirectal abscess
Treatments-
5-aminosalicylates with steroids- decrease inflammation
Immunomodulatory agents- suppress immune system
If severe- hospitalization for IV and steroids
Extreme malnutrition may require total parenteral nutrition
Surgical resection of colon
Crohn’s Disease: Inflammatory disorder that affects any part of the GI tract.
Inflammation begins in intestinal mucosa and spreads with discontinuous transmural involvement (skip lesions).
Clinical manifestations: diarrhea, bleeding, weight loss, abdominal pain, hyperalbuminuria
If ileum is involved- anemia
Polyp: Neoplastic tumorous projection of mucosal epithelium.
Most are benign
Genetic mutations associated with colorectal cancer
Promote cell proliferation→ KRAS, BRAF
Tumor suppressors→ APC, TP53, DCC at chromosome 18q
Diverticula: Herniations/sac-like outpouchings of mucosa and submucosa through muscle layers
Diverticulosis: Asymptomatic diverticular disease
Diverticulitis: Inflammation of diverticula
Diverticular disease: Outpouches of mucosa appear as sac-like openings from the mucosal surface of the open bowel.
Symptoms- cramping pain, distention, diarrhea, constipation
Treatment- increase fiber intake
Uncomplicated diverticular disease- bowel rest, clear liquid diet, analgesia, antibiotics
Complicated diverticular disease- IV antibiotics, abscess drainage
Appendicitis: Inflammation of vermiform appendage
Obstructed lumen→ Decreased blood flow→ Hypoxia→ Gangrenous necrosis→ Perforation→ Peritonitis
Liver and Pancreas
Formation of bilirubin
Red blood cell destruction→ hemoglobin→ heme→ biliverdin→ unconjugated bilirubin
Unconjugated bilirubin→ Unconjugated bilirubin albumin complex→ unconjugated bilirubin glucuronic acid→ conjugated bilirubin
Hemolytic Jaundice: Destruction of red blood cells causes excess hemoglobin to be released into the blood, and the liver then cannot process the increased amounts of unconjugated bilirubin.
Hepatocellular Jaundice: Failure of liver cells to conjugate bilirubin and of bilirubin to pass from liver to intestine.
Obstructive Jaundice: Obstruction to passage of conjugated bilirubin from liver to intestine.
Intrahepatic: due to compression of bile canaliculi.
Extrahepatic: blockage of bile duct
Liver Cirrhosis: Irreversible inflammatory disease marked by fibrosis and nodular regeneration.
Fibrosis and scarring appears at a later stage, when a person is officially experiencing cirrhosis.
Alcoholic Fatty Liver (steatosis): Alcohol metabolism leads to deposition of fat in liver.
Alcohol metabolites
Acetaldehyde damages mitochondria
Hydrogen ions promote fat accumulation
Alcoholic Hepatitis: increased hepatic fat storage, inflammation, and degeneration and necrosis of hepatocytes with infiltration of neutrophils and lymphocytes.
Portal hypertension: increased blood pressure at portal vein
Varices: dilated blood vessels that occur in venous, arterial, and lymphatic systems.
Prolonged pressure due to portal vein hypertension gets distributed through the GI tract, resulting in esophageal varices.
Ascites: Accumulation of fluid in peritoneal space.
Contributing factors- cirrhosis, heart failure, constrictive pericarditis, nephrotic syndrome
Coagulopathies, inability to clot blood, appear during liver disease because the liver produces proteins for clotting.
Acute Pancreatitis: Develops due to obstruction of outflow of pancreatic digestive enzymes caused by bile and pancreatic duct obstruction.
Leading cause- gallstones
Also results from direct cellular injury due to alcohol, drugs, infection
End goal of treatment is to stop autodigestion and prevent systemic complications.
Chronic Pancreatitis: A process of progressive fibrotic destruction and irreversible scarring of pancreas.
History of alcoholism is found in 70-75% of cases
Exocrine cell insufficiency: early in disease, maldigestion and malabsorption syndromes, steatorrhea (bulky, fatty stool)
Endocrine cell insufficiency: later in disease, diabetes mellitus (hyperglycemia)
Pancreatic cancer
Malignant adenocarcinomas- 90-95% of pancreatic cancers, derived from pancreatic duct, functionally “silent”
Risk factors- smoking, alcoholism, high fat diet, chronic pancreatitis
Poor prognosis- 5% survive 5 years