Post Type Archives: Topics

Renal Papillary Necrosis (RPN)
Renal papillary necrosis (RPN) is coagulative necrosis and sloughing off of renal papilla after ischemia or oxidative damage.
The renal papilla is the rounded apex of each medullary pyramid. Each papilla represents the confluence of the collecting ducts from each nephron within that pyramid.
The papillary tip receives only a marginal supply of blood from small-caliber vessels. The already tenuous vascular supply makes renal papilla vulnerable to ischemia and necrosis.
Etiopathogenesis
Reduced blood supply to renal papilla → Ischemia →coagulative necrosis and sloughing of renal papilla → necrosed tissue get infected or calcified → or it can slough off and obstruct urinary tract. A large amount of necrosed tissue causes acute urinary tract obstruction and renal failure.
Nephrotoxic drugs can cause renal papillary necrosis by toxic effects and oxidative damage to cells of renal papilla.
Following are the most common causes associated with RPN-
SPA D CAT because it will come on TV and teach Renal Papillary Necrosis
SPA S- sickle cell anemia P- pyelonephritis A- analgesic abuse
D-diabetes Mellitus
C-cirrhosis A-alcoholism T-tuberculosis
T- transplant rejection, thrombosis of renal vein V-vasculitis

Barrett’s esophagus is associated with chronic gastroesophageal reflux (GERD) and reflux esophagitis. Long-term acid exposure induces metaplastic changes in distal esophageal mucosa. And the esophageal squamous epithelium is replaced by columnar and goblet cells (intestinal metaplasia).
Pathogenesis
Chronic GERD → Increased acid exposure → Esophageal mucosal injury and squamous epithelial damage → Acute and chronic inflammatory changes → Reflux esophagitis → Recovery from damaged area involves metaplastic changes (Barrett’s esophagus) → Esophageal stem cells develop intestinal metaplasia (columnar and goblet cells) → Metaplasia may lead to dysplasia → Adenocarcinoma of the esophagus
Associated Risk Factors
• GERD
• Obesity
• Men > Women
Clinical Presentation of Barrett’s esophagus
• Heartburn
• Regurgitation
• Difficulty in swallowing
Diagnosis
History of chronic GERD and clinical presentation
Upper GI Endoscopy
Endoscopic examination shows tongues and patches of red, velvety mucosa extending upwards from the gastroesophageal junction. The normal esophageal mucosa looks smooth, pale, and pearly white.
Biopsy
Gastric and intestinal metaplasia is present in mucosa above the gastroesophageal junction. The presence of goblet cells with mucous vacuoles is defining feature of intestinal metaplasia. Goblet cells stain pale blue by H&E stain.

Focal segmental glomerulosclerosis (FSGS) is characterized by sclerosis of <50% of glomeruli (Focal). And sclerosis involves only a part of each affected glomerulus(segmental). The most common Primary glomerular lesions that lead to the nephrotic syndrome are focal segmental glomerulosclerosis (in adults) and minimal-change disease (in children). Types and causes FSGS can be primary and secondary. This distinction has both prognostic and therapeutic implications. Primary FSGS (idiopathic) - approximately 20% to 30% of all cases of nephrotic syndrome. Secondary FSGS may be associated with the following conditions - • HIV infection • Heroin abuse • Obesity • Sickle cell disease • Secondary to other forms of GN (e.g., IgA nephropathy, hypertensive nephropathy, reflux nephropathy) • As a maladaptation to nephron loss due to chronic kidney disease or congenital malformations • Inherited forms are associated with mutations in cytoskeletal proteins nephrin and podocin. Nephrin and podocin are essential for the integrity of podocytes. Pathogenesis Multiple factors/defects → Glomerular injury → Degeneration and Focal disruption of Podocytes →Decreased Glomerular barrier integrity →Protein and Lipid leakage →Nonselective proteinuria→ Nephrotic range >3g/day→ Protein and Lipid trapped in foci of injury →Deposition of Hyaline and Mesangial matrix→ Sclerosis of injured part of glomerulus →Segmental Sclerosis→ Focal Segmental Glomerulosclerosis.
Adaptive FSGS
Hypertension-related renal damage→ Loss of autoregulation of renal blood flow at the afferent arteriole
→Transmission of elevated pressures to an unprotected glomerulus →Leading to hyperfiltration and hypertrophy→ Increased fibrosis and sclerosis→ Eventual focal segmental glomerular sclerosis.

Morphology
Light microscopy- focal segmental sclerosis and hyalinization of glomeruli. Juxtamedullary nephrons are affected first, and inadequate sampling may miss focal lesions.
Histological Variants- FSGS is classified into five variants:
Not Otherwise Specified (NOS)- It is the most common variant of FSGS
Tip – the segmental lesion involves a tubular pole of the glomerulus.
Perihilar – sclerosis and hyalinization at the vascular pole of the glomerulus. It is present in cases with hyperfiltration and adaptive response where glomerular pressure is very high.
Cellular- hypercellular glomerulus with endocapillary and epithelial hyperplasia is characteristic of this variant.
Collapsing- is characterized by the collapse of the glomerular tuft and epithelial cell hyperplasia. It has the lowest rate of remission and the worst prognosis.
Immunofluorescence – C3 and IgM deposits in sclerotic area and mesangium.
Electron Microscopy –shows podocyte effacement and detachment with mesangial expansion.

C3 glomerulopathy is a broad term encompassing-
• dense deposit disease (DDD), former MPGN type II
• C3 glomerulonephritis
Both have low serum C3 levels (hypocomplementemia)
C3 glomerulonephritis comprises examples of MPGN types I and III, in which immunofluorescence reveals predominant C3 deposits.
Light microscopy
Both C3GN and DDD have similar Light microscopy findings.
• Hypercellular, Lobulated glomeruli
• Duplicated basement membranes in capillary walls
• ↑↑ Mesangial matrix
Immunofluorescence – Similar in both C3GN and DDD
Bright mesangial and glomerular capillary wall staining for C3. Immunoglobulins (IgG) are absent.
Electron Microscopy – (different electron dense pattern)
C3GN
Mesangial and subendothelial electron-dense “waxy” deposits of C3.
DDD
lamina densa and subendothelial space of the GBM are transformed into an irregular, ribbonlike, and extremely electron-dense structure.

Bartter syndrome is an autosomal recessive salt-wasting renal tubular disorder. It is characterized by hypokalemia, hypochloremia, metabolic alkalosis, and high renin with normal/low blood pressure. This disorder mimics chronic loop diuretic (furosemide).
It results from mutations in various genes that affect the function of ion channels and transporters that mediate transepithelial salt reabsorption in the thick ascending limb of the loop of Henle.
Etiology
Impairment in the sodium-potassium-chloride cotransporter (NKCC2) or the potassium channel (ROMK) affects the transport of sodium, potassium, and chloride in the thick ascending limb of the loop of Henle (TALH) and leads to Bartter syndrome.
Types of Bartter syndrome:
• Type I results from mutations in the sodium chloride/potassium chloride cotransporter gene (NKCC2)
• Type II results from mutations in the ROMK gene.
• Type III results from mutations in the chloride channel gene (CLC-Kb)
• Type IV results from the loss-of-function mutations in gene encoding barttin. Barttin is required for both chloride channels ClC-Kb and ClC-Ka to function.
• Type V results from mutations in extracellular calcium ion-sensing receptors and in the genes that encode the chloride channel subunits, ClC-Ka and ClC-Kb.
Pathophysiology
Bartter syndrome is a renal tubular salt-wasting disorder where a mutation in various sodium and chloride transporting channels genes leads to impaired reabsorption of sodium and chloride in the thick ascending limb of the loop of Henle.
Impaired chloride reabsorption in the thick ascending limb of the loop of Henle results in malabsorption of calcium thick ascending limb (TAL). Under normal conditions, calcium and magnesium are absorbed paracellularly under the influence of a positive charge in the lumen due to the reabsorption of negatively charged chloride ions. Increased calcium loss in urine increases the chances of Osteoporosis and Nephrocalcinosis.
Increased Distal convoluted tubular delivery of sodium, calcium, and magnesium → increased renin through JG apparatus →activation of Renin angiotensin aldosterone system →increased sodium reabsorption in DCT in exchange of potassium and hydrogen ions→ hypokalemia and metabolic alkalosis
Excessive salt and water loss →volume depletion →activation of the renin-angiotensin-aldosterone system (RAAS)
→secondary hyperaldosteronism →Long-term stimulation causes hyperplasia of the juxtaglomerular apparatus →high renin levels with normal blood pressure

Bartter Syndrome: Clinical Presentation
Signs and symptoms of Bartter syndrome are due to electrolyte imbalance, water loss, and its consequences. It mimics long-term ingestion of loop diuretics (furosemide).
In Utero
• Polyhydramnios
• Cord prolapse
• Preterm delivery
• Placental abruption
Infants
• Polyuria
• Polydipsia
• Severe dehydration
• Failure to thrive
Children and adults
• Salt craving
• Polyuria
• Polydipsia
• Normal to low blood pressure
• Failure to thrive
• Vomiting
• Abnormal facies – prominent forehead, large eyes, protruding ears, drooping mouth
• Sensorineural hearing loss
• Cardiac arrhythmias and sudden cardiac death due to electrolyte imbalances
• Osteoporosis due to calcium loss in urine
Treatment
• Tubular defects in Bartter syndrome cannot be corrected, Kidney Transplantation is the only cure.
Management goals
• Intermittent amniocentesis (draining excess amniotic fluid) to treat polyhydramnios
• Normalize potassium levels
• Treat metabolic alkalosis
• Treat and prevent dehydration – saline infusion

Pulmonary hypertension is defined as an elevation in mean pulmonary artery pressure (PAP) > 20 mm Hg or more at rest. Normal PAP levels are 8-20 mmHg.
Hemodynamic definition PH vs PAH
Pulmonary hypertension (PH) = mPAP > 20 mm of Hg at rest
Pulmonary Arterial Hypertension (PAH) has mPAP of >20 mm of Hg at rest but it has Pulmonary capillary wedge pressure (PCWP) <15 mm of Hg (normal PCWP). Right heart catheterization is the gold standard test for pulmonary artery pressure measurement. Classification Pulmonary hypertension is classified into five groups by the World Health Organization (WHO)- 1. Pulmonary arterial hypertension (PAH) is associated with heritable forms of pulmonary hypertension and diseases that cause pulmonary hypertension by affecting small pulmonary muscular arterioles. These include connective tissue diseases, human immunodeficiency virus, and congenital heart disease with a left to right shunt 2. Pulmonary hypertension due to left-sided heart disease, including systolic and diastolic dysfunction and valvular disease 3. Pulmonary hypertension due to lung diseases and/or hypoxia, including COPD and interstitial lung disease 4. Chronic thromboembolic pulmonary hypertension (CTEPH) 5. Pulmonary hypertension with unclear or multifactorial mechanisms

Budd-Chiari Syndrome (BCS) is a rare condition associated with obstruction of two or more major hepatic veins leading to hepatic venous outflow obstruction.
Etiology
Hepatic Venous Outflow obstruction in Budd-Chiari Syndrome can be due to-
• Thrombosis of Hepatic veins
• Compression / Invasion of Hepatic veins
Thrombosis of Hepatic veins
The majority of cases with Budd-Chiari Syndrome are associated with hypercoagulable states causing thrombosis in hepatic veins. The most important causes are the following-
• Polycythemia Vera/ Myeloproliferative Disorders – nearly 50% of cases with Budd-Chiari Syndrome are associated with myeloproliferative disorders (Polycythemia vera is most common).
• OCP/ Pregnancy / Post-partum period – all are hypercoagulable states
• Antiphospholipid antibody syndrome
• Paroxysmal Nocturnal hemoglobinuria (PNH)
• Clotting abnormalities
Compression/Invasion of the Hepatic Vein
• Neoplasm- Intrabdominal malignancies (HCC and RCC are most common)
• Space Occupying lesions Liver – Hepatic cyst, aspergillosis

Pathophysiology
Obstruction of two or more hepatic veins →hepatic venous outflow obstruction→ impaired blood drainage to inferior vena cava→ increased backflow of the blood →hepatic venous congestion
Hepatic venous congestion→ hepatomegaly →stretching of liver capsule →abdominal pain and tender hepatomegaly
Hepatic venous congestion→ increases sinusoidal pressure → sinusoidal dilation →reduced hepatic blood flow→ cellular hypoxia→ centrilobular necrosis and peripheral fatty degeneration (Nutmeg liver) →liver dysfunction →jaundice, hyperbilirubinemia and increased liver enzyme→ liver failure if left untreated

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Mallory-Weiss Tears: Esophageal tear
Mallory-Weiss tears are longitudinal mucosal tears in the esophageal mucosa. It is one of the common causes of acute upper gastrointestinal bleeding, and the gastroesophageal junction (gastric cardia) is the most common site.
The tear is superficial and involves only the mucosal layer, in contrast to Boerhaave’s syndrome. Boerhaave’s syndrome has full-thickness rupture (the tear involves the muscular layer).
These tears most commonly occur after the period of profuse vomiting, violent coughing, or retching and result in a short period of hematemesis.
The tear is caused by repeated acts of a sudden increase in intraabdominal pressure (IAP). The increased intraabdominal pressure is associated with retching, vomiting, straining, coughing, cardiopulmonary resuscitation (CPR), and blunt abdominal trauma.
Most commonly associated with
• Alcohol abuse (Most common 50-70%)
• Eating disorders associated with forceful retching (bulimia nervosa)
• Food poisoning
• Hiatal hernia
Pathogenesis
The sudden and rapid increase in intraabdominal pressure → Reflux of acid with pressure → Fluid flow shear stress → Longitudinal tear in mucosa → Tear may reach deep into the submucosal arteries and veins → Upper GI bleeding (Hematemesis).
The rapid increase in intraabdominal pressure may happen in-
• forceful and repeated emesis (Bulimia)
• profuse vomiting (alcoholic abuse)
• coughing
• blunt abdominal trauma
Clinical presentation
• Hematemesis- coffee ground appearance or bright red blood
• Epigastric pain
• Melena

Diffuse Esophageal Spasm (DES) is a rare motility disorder of the esophagus. It is characterized by diffuse non-peristaltic, uncoordinated spasmodic contractions in the esophagus. It leads to episodic retrosternal chest pain and intermittent dysphagia.
Etiology
There is an imbalance in the coordination of the inhibitory and excitatory postganglionic pathways. It leads to non-peristaltic spasmodic contractions. Several segments of the esophagus contract independent of each other simultaneously, causing improper propagation of the food bolus in DES. It causes intermittent dysphagia, retrosternal chest pain, regurgitation, and globus sensation.
The exact cause is unknown. The following are likely to be associated with DES-
• Acid reflux in gastroesophageal reflux disease (GERD) irritates the esophageal wall and may trigger a diffuse esophageal spasm
• Neurological disorders (neurodegenerative/ neuromuscular disorders) may lead to an imbalance between inhibitory and excitatory signals. It causes uncoordinated spasmodic contractions.
• Increased release of acetylcholine
• nitric oxide-mediated impairment of inhibitory ganglion neuronal function
• high BMI and high cholesterol levels might cause lower esophageal sphincter dysfunction and GERD
• Anxiety or depression
Clinical presentation
Episodic retrosternal chest pain can mimic heart attack/ angina. It might manifest upon eating quickly or consuming very hot or cold food.
Intermittent dysphagia- can be associated with both solid and liquid food.
Globus sensation – feeling a lump in your throat as if something is stuck in the throat.
Corkscrew or rosary beads appearance on barium study (only during episodic spasm and pain).