Patho Exam 2

Metabolic disturbances: metabolic acidosis vs metabolic alkalosis

• Key definitions

  • Metabolic acidosis: decrease in HCO₃⁻ or accumulation of non-volatile acids leading to ↓pH

  • Metabolic alkalosis: increase in HCO₃⁻ or loss of H⁺ leading to ↑pH

• Normal reference ranges (for context)

  • pH: 7.35–7.45

• Etiologies of metabolic acidosis (think MUDPILES/organic acids and loss of bicarbonate)

  • MUDPILES mnemonic (common causes): Methanol, Uremia, Diabetic ketoacidosis, Propylene glycol, Iron, Lactic acidosis, Ethylene glycol, Salicylates

  • Loss of bicarbonate: Severe diarrhea, pancreatic fistula

  • Renal failure leading to reduced acid excretion

  • Ketoacidosis: Diabetic, alcoholic, starvation

  • Ingestion of toxins causing anion-gap acidosis: Methanol, Ethylene glycol, Salicylates (in high-dose)

• Etiologies of metabolic acidosis without an anion gap (hyperchloremic)

  • Diarrhea (loss of bicarbonate with chloride retention)

  • Renal tubular acidosis

  • Early renal failure

• Etiologies of metabolic alkalosis

  • Loss of H⁺: Vomiting, nasogastric suction

  • Diuretic use (especially loop and thiazide) causing contraction alkalosis

  • Mineralocorticoid excess (e.g., Cushing’s, hyperaldosteronism)

  • Alkali administration (bicarbonate therapy)

• Compensation and diagnostic approach

  • Respiratory compensation for metabolic acidosis: hyperventilation to decrease PaCO₂

  • For metabolic alkalosis, respiratory compensation is hypoventilation to increase PaCO₂; there is no simple universal formula, but a rule of thumb: $\Delta PaCO<em>2 \approx 0.7 \times \Delta [\mathrm{HCO</em>3^-}]$

• Distinguishing features and clinical cues

  • Anion gap vs normal anion gap helps differentiate etiologies

  • Acidosis with high AG: often organic acids or toxins; acidosis with normal AG: bicarbonate loss or renal tubular acidosis

  • Serum electrolytes and bicarbonate trend guide treatment (intravenous bicarbonate in severe acidosis, treat underlying cause)

• Clinical manifestations (common and organ-system effects)

  • Metabolic acidosis: rapid breathing (Kussmaul respirations in severe cases), headache, confusion, lethargy, nausea

  • Metabolic alkalosis: hypoventilation, confusion, tingling, muscle cramps, seizures in severe cases

• Practical implications

  • Acid-base disorders reflect underlying pathophysiology; treating the underlying cause is primary

  • In diabetes management, monitor for ketoacidosis (metabolic acidosis with high AG)

• Examples/hypothetical scenarios

  • A patient with diarrhea develops non-AG metabolic acidosis due to bicarbonate loss

  • A patient with vomiting develops metabolic alkalosis due to H⁺ loss and volume contraction

Endocrinology: feedback loops and hormone roles

• Feedback loops in endocrinology

  • Negative feedback loop

  • Core principle: downstream hormone inhibits upstream signal to maintain homeostasis

  • Classic example: Hypothalamic-pituitary-adrenal (HPA) axis

    • CRH from hypothalamus stimulates ACTH release from anterior pituitary

    • ACTH stimulates cortisol release from adrenal cortex

    • Increased cortisol exerts negative feedback on both hypothalamus (CRH) and pituitary (ACTH) to reduce further release

  • Positive feedback loop

  • Core principle: downstream signal amplifies upstream signal

  • Classic examples: Estrogen-induced LH surge triggering ovulation (positive feedback on GnRH/LH axis); oxytocin release during labor amplifying contractions through positive feedback on the uterus

• Hormones: functions and key relationships

  • ACTH (Adrenocorticotropic hormone)

  • Stimulates adrenal cortex to secrete cortisol

  • Regulation via CRH from hypothalamus; cortisol provides negative feedback to both hypothalamus and pituitary

  • Cortisol (glucocorticoid)

  • Increases glucose production, supports gluconeogenesis, and modulates metabolism; anti-inflammatory effects

  • Stress response mediator; modulates vascular responsiveness

  • Growth Hormone (GH)

  • Stimulates growth and protein synthesis; stimulates liver to produce IGF-1

  • Metabolic effects: promotes lipolysis, antagonizes insulin in some tissues

  • Antidiuretic Hormone (ADH, vasopressin)

  • Increases water reabsorption in renal collecting ducts via aquaporin-2 channels

  • Regulated by plasma osmolality and volume status

  • T3/T4 (thyroid hormones)

  • Regulation of basal metabolic rate, protein synthesis, thermogenesis, and development

  • T4 is a prohormone converted to the more active T3 in tissues

  • Calcitonin

  • Secreted by thyroid C-cells; lowers blood calcium by inhibiting osteoclast activity (less bone resorption)

  • Insulin

  • Secreted by pancreatic beta cells; lowers blood glucose by promoting cellular uptake of glucose, glycolysis, lipogenesis, and protein synthesis

  • Opposed by glucagon (secreted by α-cells) which raises blood glucose by promoting gluconeogenesis and glycogenolysis

• Significance and clinical relevance

  • Dysregulation of feedback loops underlies diseases like Cushing’s (excess cortisol) and Addison’s (adrenal insufficiency)

  • Understanding hormonal hierarchies aids interpretation of lab patterns and treatment approaches (e.g., ACTH stimulation tests, thyroid function tests)

Disease dossiers: definitions, pathophysiology, risk factors, and clinical cues

Acute and chronic gastritis

• Definitions

  • Acute gastritis: sudden inflammation of the gastric mucosa

  • Chronic gastritis: long-standing inflammation with potential mucosal atrophy

• Pathophysiology

  • H. pylori infection is a common cause; NSAID use damages mucosal barriers; autoimmune gastritis involves autoantibodies to parietal cells/IF

• Risk factors

  • NSAID/aspirin use, alcohol use, smoking, older age, H. pylori exposure, autoimmune history

• Clinical manifestations

  • Epigastric pain or burning, nausea, vomiting, anorexia; possible occult GI bleeding

GERD (gastroesophageal reflux disease)

• Pathophysiology

  • Transient relaxation or incompetence of lower esophageal sphincter; reflux of gastric contents into esophagus

• Risk factors

  • Obesity, hiatal hernia, pregnancy, delayed gastric emptying, certain dietary triggers (fatty meals, caffeine, alcohol)

• Clinical manifestations

  • Heartburn, regurgitation, dysphagia, nighttime symptoms; possible chronic cough or laryngitis

• Complications

  • Esophagitis, stricture, Barrett’s esophagus (metaplasia; risk for esophageal adenocarcinoma)

Acute and chronic pancreatitis

• Pathophysiology

  • Autodigestion of pancreas due to premature activation of pancreatic enzymes; inflammation leads to edema and fat necrosis

• Etiologies/risk factors

  • Gallstones, alcohol use, medications, hypertriglyceridemia, genetic predispositions

• Clinical manifestations

  • Sudden, severe epigastric pain radiating to back; nausea/vomiting; abdominal tenderness

Diverticulitis vs Diverticulosis

• Diverticulosis

  • Definition: presence of diverticula (pouches) in colonic wall, often asymptomatic

  • Risk factors: low-fiber diet, aging

• Diverticulitis

  • Definition: inflammation/infection of diverticula

  • Clinical cues: LLQ pain, fever, leukocytosis

• Diverticulosis vs diverticulitis connections

  • Dietary fiber impacts risk of progression from diverticulosis to diverticulitis

Inflammatory Bowel Disease (IBD): Crohn’s Disease vs Ulcerative Colitis

• Crohn’s Disease (CD)

  • Pathophysiology: transmural inflammation; skip lesions; can involve any part of GI tract; granulomas possible

  • Clinical features: abdominal pain, chronic diarrhea, weight loss, malabsorption; may have fistulas or strictures

  • Distribution: ileum and colon common; any segment of GI tract possible

• Ulcerative Colitis (UC)

  • Pathophysiology: continuous mucosal inflammation starting in the rectum and extending proximally; no small bowel involvement; no granulomas

  • Clinical features: bloody diarrhea, abdominal pain, urgency, tenesmus

• Comparisons

  • CD: transmural, non-contiguous disease; fistulas; growth failure in children

  • UC: mucosal, contiguous disease; colon-only; higher risk of toxic megacolon

• Complications and management

  • Both: risk of colorectal cancer with long-standing disease; extraintestinal manifestations; immunomodulatory therapy and biologics; surgical options in refractory disease

Hepatitis A, B, C

• Transmission examples and general features

  • Hepatitis A (HAV): fecal-oral route (contaminated food/water); typically acute, no chronic carrier state

  • Hepatitis B (HBV): parenteral exposure; blood, sex; risk of chronic infection in some individuals; vaccination available

  • Hepatitis C (HCV): primarily bloodborne transmission (needles, transfusions prior to screening); often becomes chronic; antiviral therapy available

• Clinical timelines and management

  • Acute hepatitis: jaundice, fatigue, RUQ discomfort; labs show elevated ALT/AST; supportive care; vaccination for A and B

  • Chronic hepatitis B/C: potential progression to cirrhosis or hepatocellular carcinoma if untreated; antiviral therapies available for HBV/HCV

Incontinence types

• Stress incontinence

  • Mechanism: increased intra-abdominal pressure causes leakage (often with coughing, sneezing); commonly due to pelvic floor weakness

• Urge incontinence

  • Mechanism: overactive detrusor; involuntary detrusor contractions; usually overnight or frequent urge to urinate

• Functional incontinence

  • Mechanism: physical or cognitive impairments prevent timely bathroom access

• Overflow incontinence

  • Mechanism: underactive detrusor or bladder outlet obstruction leading to chronic urinary retention

• Neurogenic incontinence

  • Mechanism: nervous system injuries/diseases disrupting bladder control

Urinary tract infection (UTI)

• Pathophysiology

  • Ascending infection from periurethral area to bladder; may involve ureters/kidneys

• Risk factors

  • Female anatomy, urinary stasis, catheterization, sexual activity, diabetes, menopause

• Clinical manifestations

  • Dysuria, frequency, urgency, suprapubic pain; fever and flank pain with pyelonephritis

Urolithiasis (kidney stones)

• Pathophysiology

  • Supersaturation of urinary solutes leading to crystal formation and stone development

• Common stone types

  • Calcium oxalate/phosphate, uric acid, struvite, cystine

• Risk factors

  • Dehydration, dietary factors, hypercalciuria, gout, metabolic disorders

• Clinical cues

  • Sudden, severe flank or groin pain, colicky, hematuria

Pyelonephritis

• Pathophysiology

  • Ascending infection from lower urinary tract to renal pelvis and parenchyma

• Risk factors

  • Female sex, vesicoureteral reflux, obstruction, diabetes

• Clinical manifestations

  • Fever, flank pain, nausea/vomiting, costovertebral angle tenderness

Polycystic kidney disease (PKD)

• Pathophysiology

  • Genetic disorders (autosomal dominant most common) causing cyst formation in kidneys

• Clinical features

  • Hypertension, flank pain, progressive renal failure, family history

• Complications

  • Berry aneurysms, hepatic cysts

Chronic renal failure (CRF)

• Definition and progression

  • Chronic kidney disease stages leading to reduced glomerular filtration rate (GFR)

• Risk factors

  • Diabetes mellitus, hypertension, glomerulonephritis, polyscystic kidney disease

• Clinical manifestations

  • Fatigue, edema, electrolyte disturbances (hyperkalemia, metabolic acidosis), anemia, uremic symptoms as it advances

Endocrine/metabolic disorders of growth and thyroid/parathyroid systems

Acromegaly, gigantism, dwarfism

• Definitions and timing

  • Gigantism: excess GH before epiphyseal closure -> tall stature; acromegaly: excess GH after closure -> proportional overgrowth of hands, feet, facial features

  • Dwarfism: short stature due to GH deficiency or other etiologies

• Etiology and pathophysiology

  • Pituitary adenoma is a common cause of GH excess; GH/IGF-1 axis dysregulation

• Clinical cues and diagnosis

  • Gigantism/acromegaly: coarsened facial features, enlarged hands/feet, glucose intolerance; IGF-1 levels and oral glucose suppression test

Hypothyroidism vs hyperthyroidism

• Hypothyroidism

  • Deficiency of thyroid hormones; common causes include Hashimoto thyroiditis, iodine deficiency; symptoms: fatigue, weight gain, cold intolerance, constipation, bradycardia

• Hyperthyroidism

  • Excess thyroid hormones; common causes include Graves’ disease, toxic multinodular goiter; symptoms: weight loss, heat intolerance, palpitations, tremor, anxiety

Hyperparathyroidism vs hypoparathyroidism

• Hyperparathyroidism

  • Excess parathyroid hormone (PTH) leading to hypercalcemia and hypophosphatemia; primary cause often adenoma

• Hypoparathyroidism

  • Deficient PTH leading to hypocalcemia and hyperphosphatemia; causes include inadvertent surgical removal

• Clinical implications

  • Hypercalcemia symptoms (stones, bones, groans, thrones, psychiatric overtones); hypocalcemia signs include tingling, tetany, Chvostek sign

Diabetes insipidus (DI) vs Syndrome of inappropriate ADH (SIADH)

• Diabetes insipidus (DI)

  • Definition: deficiency of ADH or renal insensitivity leading to polyuria and polydipsia; hypernatremia risk if water intake is insufficient

• SIADH

  • Definition: excessive ADH causing water retention with hyponatremia and concentrated urine despite low serum osmolality

• Clinical cues

  • DI: dilute urine, high serum osmolality

  • SIADH: hyponatremia with euvolemia

Cushing’s Disease vs Addison’s Disease

• Cushing’s Disease

  • Pituitary ACTH-secreting adenoma causing hypercortisolism

  • Features: weight gain, moon face, buffalo hump, hypertension, glucose intolerance; may have hirsutism and mood changes

• Addison’s Disease

  • Primary adrenal insufficiency (adrenal cortex destruction or dysfunction)

  • Features: fatigue, weight loss, hyperpigmentation, hypotension, hyponatremia, hyperkalemia

Type 1 vs Type 2 diabetes mellitus – complications and similarities/differences

• Type 1 Diabetes Mellitus (T1DM)

  • Autoimmune destruction of pancreatic beta cells leading to insulin deficiency

  • Typically onset in childhood/adolescence; acute presentation with polyuria, polydipsia, weight loss, diabetic ketoacidosis risk

• Type 2 Diabetes Mellitus (T2DM)

  • Insulin resistance with relative insulin deficiency; often associated with obesity and metabolic syndrome; gradual onset

• Similarities

  • Hyperglycemia, long-term vascular complications, risk of cardiovascular disease, need for lifestyle modification and pharmacotherapy

• Differences

  • Etiology (autoimmune vs insulin resistance), age of onset, and typical clinical trajectory; T2DM may have a gradual progression; T1DM requires lifelong insulin therapy

• Complications of diabetes (covering both T1D and T2D)

  • Microvascular: retinopathy (potential blindness), nephropathy (proteinuria, CKD), neuropathy (peripheral, autonomic)

  • Macrovascular: accelerated atherosclerosis leading to coronary artery disease, stroke, peripheral vascular disease

  • Other: increased infection risk, wound healing impairment, diabetic ketoacidosis (T1D) or hyperosmolar hyperglycemic state (HHS) risk in T2D

  $$\text{AG} = [\mathrm{Na}^+] - ([\mathrm{Cl}^-] + [\ma